RESUMEN
BACKGROUND: Nasopharyngeal carcinoma (NPC) is diagnosed relatively late and has a poor prognosis, requiring early detection to reduce the disease burden. This diagnostic test accuracy meta-analysis evaluated the serological diagnostic value of nine EBV-related IgA antibody panels (EBNA1-IgA, VCA-IgA, EA-IgA, Zta-IgA, EBNA1-IgA + VCA-IgA, VCA-IgA + EA-IgA, VCA-IgA + Rta-IgG, EBNA1-IgA + VCA-IgA + Zta-IgA and VCA-IgA + EA-IgA + Rta-IgG), aiming to identify suitable serological detection biomarkers for NPC screening. METHODS: PubMed, Embase, China National Knowledge Infrastructure and Chinese BioMedical Literature Database were searched from January 1st, 2000 to September 30th, 2023, with keywords nasopharyngeal carcinoma, IgA, screening, early detection, early diagnosis, sensitivity and specificity. Articles on the diagnostic value of serum EBV-related IgA antibody panels for NPC were included. Study selection, data extraction, and quality assessment were performed independently by two researchers, and a third researcher was consulted in the case of disagreement. Bivariate models were used for statistical analysis. The quality of included studies was evaluated through Quality Assessment of Diagnostic Accuracy Studies tool (QUADAS-2). RESULTS: A total of 70 articles were included, involving 11 863 NPC cases and 34 995 controls. Among the nine EBV-related IgA antibody panels, EBNA1-IgA + VCA-IgA [0.928 (0.898, 0.950)], VCA-IgA + Rta-IgG [0.925 (0.890, 0.949)], EBNA1-IgA + VCA-IgA + Zta-IgA [0.962 (0.909, 0.985)] and VCA-IgA + EA-IgA + Rta-IgG [0.945 (0.918, 0.964)] demonstrated higher pooled sensitivity (95%CI). In terms of diagnostic odds ratio (DOR) (95%CI), EBNA1-IgA + VCA-IgA [107.647 (61.173, 189.430)], VCA-IgA + Rta-IgG [105.988 (60.118, 186.857)] and EBNA1-IgA + VCA-IgA + Zta-IgA [344.450 (136.351, 870.153)] showed superior performance. Additionally, the SROC curves for EBNA1-IgA + VCA-IgA and VCA-IgA + Rta-IgG were more favorable. However, publication bias was detected for VCA-IgA (P = 0.005) and EBNA1-IgA + VCA-IgA (P = 0.042). CONCLUSIONS: In general, parallel detection of serum EBNA1-IgA, VCA-IgA and Zta-IgA antibodies using ELISA demonstrates better pooled sensitivity and DOR among the studied panels. In the cases where fewer indicators are used, serum VCA-IgA and EBNA1-IgA/Rta-IgG antibody panel exhibits a comparable performance. TRIAL REGISTRATION: The International Prospective Register of Systematic Reviews registration number: CRD42023426984, registered on May 28, 2023.
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Anticuerpos Antivirales , Infecciones por Virus de Epstein-Barr , Inmunoglobulina A , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Humanos , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Biomarcadores de Tumor/sangre , Biomarcadores de Tumor/inmunología , Detección Precoz del Cáncer/métodos , Infecciones por Virus de Epstein-Barr/inmunología , Infecciones por Virus de Epstein-Barr/diagnóstico , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/sangre , Antígenos Nucleares del Virus de Epstein-Barr/inmunología , Herpesvirus Humano 4/inmunología , Inmunoglobulina A/sangre , Inmunoglobulina A/inmunología , Carcinoma Nasofaríngeo/diagnóstico , Carcinoma Nasofaríngeo/inmunología , Carcinoma Nasofaríngeo/virología , Carcinoma Nasofaríngeo/sangre , Neoplasias Nasofaríngeas/diagnóstico , Neoplasias Nasofaríngeas/inmunología , Neoplasias Nasofaríngeas/sangre , Neoplasias Nasofaríngeas/virología , Sensibilidad y Especificidad , Pruebas Serológicas/métodosRESUMEN
Changes in metabolic characteristics are important features of tumor progression and prognosis, including nasopharyngeal carcinoma (NPC). Identifying serum metabolites as potential diagnostic and chemoradiotherapy response biomarkers for NPC is therefore crucial. In this study, ultra-performance liquid chromatography coupled with linear ion trap quadrupole orbitrap high-resolution mass spectrometry (UPLC-LTQ-Orbitrap MS) was used to analyze metabolic variations among controls, NPC patients, and NPC patients undergoing chemoradiotherapy (CRT). Univariate and multivariate analyses revealed seven differential metabolites between the control and NPC groups and eleven metabolites between the CRT and NPC groups. Five common metabolites, gluconic acid, palmitic acid, LysoPC (15:0/0:0), stearic acid, and LysoPC (20:2(11Z,14Z)/0:0), were consistently altered across groups. Notably, the first four metabolites were adjusted closer to normal after chemoradiotherapy, while this change is not reflected at LysoPC (20:2(11Z,14Z)/0:0). These common metabolites were enriched in five pathways. These findings underscore the importance of serum metabolite profiling in NPC diagnosis and treatment response assessment and offer a promising foundation for further clinical research.
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Biomarcadores de Tumor , Quimioradioterapia , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo/terapia , Carcinoma Nasofaríngeo/sangre , Carcinoma Nasofaríngeo/diagnóstico , Quimioradioterapia/métodos , Neoplasias Nasofaríngeas/sangre , Neoplasias Nasofaríngeas/diagnóstico , Neoplasias Nasofaríngeas/terapia , Masculino , Biomarcadores de Tumor/sangre , Persona de Mediana Edad , Femenino , Cromatografía Líquida de Alta Presión/métodos , Adulto , Metabolómica/métodos , AncianoRESUMEN
PURPOSE: To explore the influence of circulating lymphocyte subsets, serum markers, clinical factors, and their impact on overall survival (OS) in locally advanced nasopharyngeal carcinoma (LA-NPC). Additionally, to construct a nomogram predicting OS for LA-NPC patients using independent prognostic factors. METHODS: A total of 530 patients with LA-NPC were included in this study. In the training cohort, Cox regression analysis was utilized to identify independent prognostic factors, which were then integrated into the nomogram. The concordance index (C-index) was calculated for both training and validation cohorts. Schoenfeld residual analysis, calibration curves, and decision curve analysis (DCA) were employed to evaluate the nomogram. Kaplan-Meier methods was performed based on risk stratification using the nomogram. RESULTS: A total of 530 LA-NPC patients were included. Multivariate Cox regression analysis revealed that the circulating CD8+T cell, platelet-to-lymphocyte ratio (PLR), lactate dehydrogenase (LDH), albumin (ALB), gender, and clinical stage were independent prognostic factors for LA-NPC (p < 0.05). Schoenfeld residual analysis indicated overall satisfaction of the proportional hazards assumption for the Cox regression model. The C-index of the nomogram was 0.724 (95% CI: 0.669-0.779) for the training cohort and 0.718 (95% CI: 0.636-0.800) for the validation cohort. Calibration curves demonstrated good correlation between the model and actual survival outcomes. DCA confirmed the clinical utility enhancement of the nomogram over the TNM staging system. Significant differences were observed in OS among different risk stratifications. CONCLUSION: Circulating CD8+ T cell, PLR, LDH, ALB, gender and clinical stage are independent prognostic factors for LA-NPC. The nomogram and risk stratification constructed in this study effectively predict OS in LA-NPC.
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Linfocitos T CD8-positivos , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Nomogramas , Humanos , Masculino , Femenino , Persona de Mediana Edad , Carcinoma Nasofaríngeo/mortalidad , Carcinoma Nasofaríngeo/sangre , Carcinoma Nasofaríngeo/patología , Pronóstico , Neoplasias Nasofaríngeas/mortalidad , Neoplasias Nasofaríngeas/sangre , Neoplasias Nasofaríngeas/patología , Adulto , Anciano , Plaquetas/patología , Tasa de Supervivencia , Estudios Retrospectivos , Linfocitos/patología , Adulto JovenRESUMEN
BACKGROUND: Recently, the hemoglobin to albumin ratio (HAR) has been shown to be closely associated with the survival of certain malignancies. However, its prognostic value in nasopharyngeal carcinoma (NPC) remained to be elucidated. Herein, we aimed to explore the correlation between HAR and overall survival (OS) in NPC patients treated with concurrent chemoradiotherapy (CCRT). METHODS: This retrospective study included a total of 858 patients with NPC receiving CCRT between January 2010 and December 2014 in Sun Yat-sen University Cancer Center. We randomly divided them into the training cohort (N = 602) and the validation cohort (N = 206). We performed univariate and multivariate Cox regression analyses to identify variables associated with OS, based on which, a predictive nomogram was constructed and assessed. RESULTS: In both the training and validation cohorts, patients were classified into low- and high-HAR groups according to the cutoff value determined by the maximally selected rank statistics. This HAR cutoff value effectively divided patients into two distinct prognostic groups with significant differences. Multivariable Cox analysis revealed that higher T-stage, N-stage, and HAR values were significantly related to poorer prognosis in NPC patients and served as independent prognostic factors for NPC. Based on these, a predictive model was constructed and graphically presented as a nomogram, whose predictive performance is satisfactory with a C-index of 0.744 [95%CI: 0.679-0.809] and superior to traditional TNM staging system [C-index = 0.609, 95%CI: 0.448-0.770]. CONCLUSION: The HAR value was an independent predictor for NPC patients treated with CCRT, the predictive model based on HAR with superior predictive performance than traditional TNM staging system might improve individualized survival predictions.
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Quimioradioterapia , Hemoglobinas , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Nomogramas , Humanos , Masculino , Femenino , Persona de Mediana Edad , Quimioradioterapia/métodos , Carcinoma Nasofaríngeo/terapia , Carcinoma Nasofaríngeo/mortalidad , Carcinoma Nasofaríngeo/patología , Carcinoma Nasofaríngeo/sangre , Hemoglobinas/análisis , Pronóstico , Estudios Retrospectivos , Neoplasias Nasofaríngeas/terapia , Neoplasias Nasofaríngeas/mortalidad , Neoplasias Nasofaríngeas/patología , Neoplasias Nasofaríngeas/sangre , Adulto , Estadificación de Neoplasias , Anciano , Albúmina Sérica/análisisRESUMEN
Recurrence risks of cancer patient can change during treatment as a result of treatment-related tumor evolution. However, biomarkers that can monitor these changes are lacking. Here, we investigated whether tracking circulating tumor DNA (ctDNA) dynamics through liquid biopsy can inform real-time recurrence risk. Nasopharyngeal carcinoma (NPC) provides an ideal model where cell-free Epstein-Barr virus (EBV) DNA (cfEBV DNA), a ctDNA, can be sensitively detected. We conducted the EP-SEASON study (NCT03855020) and prospectively recruited 1,000 NPC patients undergoing per-protocol cfEBV DNA assessments at 11 time points and receiving sequential chemo-radiotherapy. Longitudinal cfEBV DNA displayed distinct patterns during neoadjuvant chemotherapy and radiotherapy. Despite the prognostic significance of cfEBV DNA at each time point, real-time recurrence risks changed in sync with cfEBV DNA dynamics. Furthermore, we identified phenotypes of whole-course ctDNA changing dynamics associated with different survival outcomes. In conclusion, tracking longitudinal on-treatment ctDNA can forecast real-time recurrence risk, facilitating risk-adapted, individualized patient management.
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Biomarcadores de Tumor , ADN Tumoral Circulante , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Recurrencia Local de Neoplasia , Humanos , ADN Tumoral Circulante/sangre , ADN Tumoral Circulante/genética , Masculino , Femenino , Biomarcadores de Tumor/sangre , Biomarcadores de Tumor/genética , Persona de Mediana Edad , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/sangre , Carcinoma Nasofaríngeo/sangre , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/virología , Carcinoma Nasofaríngeo/diagnóstico , Adulto , Neoplasias Nasofaríngeas/sangre , Neoplasias Nasofaríngeas/virología , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/diagnóstico , Estudios Longitudinales , ADN Viral/sangre , Estudios Prospectivos , Anciano , Pronóstico , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/aislamiento & purificación , Biopsia Líquida/métodos , Infecciones por Virus de Epstein-Barr/sangre , Infecciones por Virus de Epstein-Barr/virología , Infecciones por Virus de Epstein-Barr/complicacionesAsunto(s)
Fluorodesoxiglucosa F18 , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Tomografía Computarizada por Tomografía de Emisión de Positrones , Humanos , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Pronóstico , Carcinoma Nasofaríngeo/sangre , Carcinoma Nasofaríngeo/diagnóstico por imagen , Carcinoma Nasofaríngeo/patología , Neoplasias Nasofaríngeas/sangre , Neoplasias Nasofaríngeas/diagnóstico por imagen , Neoplasias Nasofaríngeas/patología , Biomarcadores de Tumor/sangre , Radiofármacos , Metástasis de la NeoplasiaRESUMEN
PURPOSE: Patients with recurrent or metastatic nasopharyngeal carcinoma (RM-NPC) have proven benefit from anti-programmed cell death 1 (anti-PD-1) monotherapy. Here, we retrospectively analyze the association of plasma Epstein-Barr virus (EBV) DNA load and tumor viral lytic genome with clinical outcome from 2 registered phase I trials. METHODS: Patients with RM-NPC from Checkmate 077 (nivolumab phase I trial in China) and Camrelizumab phase I trial between March 2016 and January 2018 were enrolled. Baseline EBV DNA titers were tested in 68 patients and EBV assessment was performed in 60 patients who had at least 3 post-baseline timepoints of EBV data and at least 1 post-baseline timepoint of radiographic assessment. We defined "EBV response" as 3 consecutive timepoints of load below 50% of baseline, and "EBV progression" as 3 consecutive timepoints of load above 150% of baseline. Whole-exome sequencing was performed in 60 patients with available tumor samples. RESULTS: We found that the baseline EBV DNA load was positively correlated with tumor size (spearman p < 0.001). Both partial response (PR) and stable disease (SD) patients had significantly lower EBV load than progression disease (PD) patients. EBV assessment was highly consistent with radiographic evaluation. Patients with EBV response had significantly improved overall survival (OS) than patients with EBV progression (log-rank p = 0.004, HR = 0.351 [95% CI: 0.171-0.720], median 22.5 vs. 11.9 months). The median time to initial EBV response and progression were 25 and 36 days prior to initial radiographic response and progression, respectively. Patients with high levels of EBV lytic genomes at baseline, including BKRF2, BKRF3 and BKRF4, had better progression-free survival (PFS) and OS. CONCLUSION: In summary, early clearance of plasma EBV DNA load and high levels of lytic EBV genes were associated with better clinical outcome in patients with RM-NPC receiving anti-PD-1 monotherapy.
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ADN Viral , Infecciones por Virus de Epstein-Barr , Herpesvirus Humano 4 , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Recurrencia Local de Neoplasia , Nivolumab , Carga Viral , Humanos , Herpesvirus Humano 4/genética , Carcinoma Nasofaríngeo/virología , Carcinoma Nasofaríngeo/tratamiento farmacológico , Carcinoma Nasofaríngeo/sangre , Carcinoma Nasofaríngeo/patología , Masculino , Femenino , Persona de Mediana Edad , ADN Viral/sangre , Neoplasias Nasofaríngeas/virología , Neoplasias Nasofaríngeas/tratamiento farmacológico , Neoplasias Nasofaríngeas/sangre , Neoplasias Nasofaríngeas/patología , Infecciones por Virus de Epstein-Barr/virología , Infecciones por Virus de Epstein-Barr/sangre , Estudios Retrospectivos , Adulto , Recurrencia Local de Neoplasia/virología , Nivolumab/uso terapéutico , Genoma Viral , Anciano , Anticuerpos Monoclonales Humanizados/uso terapéutico , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Pronóstico , Resultado del TratamientoRESUMEN
BACKGROUND: Epstein-Barr virus (EBV) is a major cause of nasopharyngeal carcinoma (NPC) and measurement of different EBV antibodies in blood may improve early detection of NPC. Prospective studies can help assess the roles of different EBV antibodies in predicting NPC risk over time. METHODS: A case-cohort study within the prospective China Kadoorie Biobank of 512â715 adults from 10 (including two NPC endemic) areas included 295 incident NPC cases and 745 subcohort participants. A multiplex serology assay was used to quantify IgA and IgG antibodies against 16 EBV antigens in stored baseline plasma samples. Cox regression was used to estimate adjusted hazard ratios (HRs) for NPC and C-statistics to assess the discriminatory ability of EBV-markers, including two previously identified EBV-marker combinations, for predicting NPC. RESULTS: Sero-positivity for 15 out of 16 EBV-markers was significantly associated with higher NPC risk. Both IgA and IgG antibodies against the same three EBV-markers showed the most extreme HRs, i.e. BGLF2 (IgA: 124.2 (95% CI: 63.3-243.9); IgG: 8.6 (5.5-13.5); LF2: [67.8 (30.0-153.1), 10.9 (7.2-16.4)]); and BFRF1: 26.1 (10.1-67.5), 6.1 (2.7-13.6). Use of a two-marker (i.e. LF2/BGLF2 IgG) and a four-marker (i.e. LF2/BGLF2 IgG and LF2/EA-D IgA) combinations yielded C-statistics of 0.85 and 0.84, respectively, which persisted for at least 5 years after sample collection in both endemic and non-endemic areas. CONCLUSIONS: In Chinese adults, plasma EBV markers strongly predict NPC occurrence many years before clinical diagnosis. LF2 and BGLF2 IgG could identify NPC high-risk individuals to improve NPC early detection in community and clinical settings.
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Anticuerpos Antivirales , Detección Precoz del Cáncer , Infecciones por Virus de Epstein-Barr , Herpesvirus Humano 4 , Inmunoglobulina A , Inmunoglobulina G , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Humanos , Masculino , China/epidemiología , Femenino , Persona de Mediana Edad , Herpesvirus Humano 4/inmunología , Estudios Prospectivos , Anticuerpos Antivirales/sangre , Carcinoma Nasofaríngeo/virología , Carcinoma Nasofaríngeo/sangre , Carcinoma Nasofaríngeo/inmunología , Carcinoma Nasofaríngeo/epidemiología , Neoplasias Nasofaríngeas/virología , Neoplasias Nasofaríngeas/sangre , Neoplasias Nasofaríngeas/inmunología , Neoplasias Nasofaríngeas/epidemiología , Infecciones por Virus de Epstein-Barr/inmunología , Infecciones por Virus de Epstein-Barr/epidemiología , Infecciones por Virus de Epstein-Barr/sangre , Adulto , Inmunoglobulina A/sangre , Detección Precoz del Cáncer/métodos , Inmunoglobulina G/sangre , Anciano , Estudios de Casos y Controles , Modelos de Riesgos Proporcionales , Pueblos del Este de AsiaRESUMEN
BACKGROUND AND PURPOSE: To develop and validate a prognostic nomogram based on pretreatment 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET-CT)radiomics parameters and peripheral blood markers for risk stratification in patients with de novo metastatic nasopharyngeal carcinoma (dmNPC). MATERIALS AND METHODS: A total of 558 patients with dmNPC were retrospectively enrolled between 2011 and 2019. Eligible patients were randomly divided into training and validation cohorts (7:3 ratio). A Cox regression model was used to identify prognostic factors for overall survival (OS). The predictive accuracy and discriminative ability of the prognostic nomogram were determined using the concordance index (C-index) and calibration curve. RESULTS: Independent factors derived from multivariable analysis of the training cohort to predict death were lactate dehydrogenase levels, pretreatment Epstein-Barr virus DNA, total lesion glycolysis of locoregional lesions, number of metastatic lesions, and age, all of which were assembled into a nomogram with (nomogram B) or without PET-CT parameters (nomogram A). The C-index of nomogram B for predicting death was 0.70, which was significantly higher than the C-index values for nomogram A. Patients were then stratified into low- and high-risk groups based on the scores calculated using nomogram B for OS. The median OS was significantly higher in the low-risk group than in the high-risk group (69.60 months [95 % CI: 58.50-108.66] vs. 21.40 months [95 % CI: 19.20-23.90]; pï¼0.01). All the results were confirmed in the validation cohort. CONCLUSION: The proposed nomogram including PET-CT parameters yielded accurate prognostic predictions for patients with dmNPC, enabling effective risk stratification for these patients.
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Fluorodesoxiglucosa F18 , Carcinoma Nasofaríngeo , Nomogramas , Tomografía Computarizada por Tomografía de Emisión de Positrones , Humanos , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Masculino , Femenino , Carcinoma Nasofaríngeo/sangre , Carcinoma Nasofaríngeo/diagnóstico por imagen , Carcinoma Nasofaríngeo/patología , Carcinoma Nasofaríngeo/mortalidad , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Adulto , Neoplasias Nasofaríngeas/sangre , Neoplasias Nasofaríngeas/diagnóstico por imagen , Neoplasias Nasofaríngeas/patología , Anciano , Metástasis de la Neoplasia , Biomarcadores de Tumor/sangre , RadiofármacosRESUMEN
To investigate the expression of Inhibin B between various clinical stages, Chinese medicine dialectic typing, and in nasopharyngeal carcinoma (NPC) tissues and serum, and to evaluate the potential of Inhibin B as a new biomarker for NPC. Paraffin specimens of pathologically confirmed NPC tissues and paracancerous tissues were retrospectively collected, and the expression of Inhibin α (INHA) and Inhibin ßB (INHBB) was detected by SP method, and their relationship with clinicopathological indexes was analyzed; in addition, patients with NPC who had received radiotherapy were included as the study subjects, and Epstein-Barr virus DNA (EBV-DNA), INHA, and INHBB in patients were detected by using the fluorescence quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, and chemiluminescent immuno-sandwiching method, respectively. EBV-DNA, EBV-viral capsid antigen-immunoglobulin A (VCA IgA), INHA, and INHBB were detected in the patients, respectively, and their relationships with traditional Chinese medicine (TCM) patterns were also analyzed. The expression of INHA and INHBB in NPC tissues was lower than that in paracancerous tissues, and the expression of INHA in NPC patients was correlated with lymphatic metastasis, clinical staging, and TCM staging; the levels of EBV-DNA and VCA IgA were higher than that of healthy populations in NPC patients and were higher than that of patients with stage IIIâ +â IV than that of patients with stage Iâ +â II, and the levels of INHA and INHBB were lower than those of healthy populations and were lower than those of patients with stage IIIâ +â IV than that of patients with stage Iâ +â II. The levels of INHA and INHBB in nasopharyngeal cancer patients were lower than those in healthy people, and the levels in stage IIIâ +â IV patients were lower than those in stage Iâ +â II patients. The levels of EBV-DNA and VCA IgA in nasopharyngeal cancer patients were correlated with the Chinese medicine patterns, and had different patterns. The expression of Inhibin B may be related to the progression of NPC, and it has certain typing significance for different TCM syndromes of NPC, which is helpful for TCM typing diagnosis.
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Medicina Tradicional China , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Humanos , Masculino , Femenino , Neoplasias Nasofaríngeas/virología , Neoplasias Nasofaríngeas/diagnóstico , Neoplasias Nasofaríngeas/sangre , Neoplasias Nasofaríngeas/patología , Carcinoma Nasofaríngeo/diagnóstico , Carcinoma Nasofaríngeo/virología , Carcinoma Nasofaríngeo/sangre , Carcinoma Nasofaríngeo/metabolismo , Carcinoma Nasofaríngeo/patología , Medicina Tradicional China/métodos , Persona de Mediana Edad , Estudios Retrospectivos , Adulto , ADN Viral/análisis , ADN Viral/sangre , Inhibinas/sangre , Herpesvirus Humano 4/genética , Biomarcadores de Tumor/metabolismo , Biomarcadores de Tumor/sangre , Estadificación de Neoplasias , Subunidades beta de Inhibinas/metabolismo , Subunidades beta de Inhibinas/sangre , Anciano , Antígenos Virales/sangre , Inmunoglobulina A/sangre , Proteínas de la CápsideRESUMEN
BACKGROUND AND OBJECTIVES: This investigation explores the clinical significance of integrating serum lactate dehydrogenase (LDH) with a multivariate model for assessing the short-term prognosis of primary nasopharyngeal carcinoma (NPC). Epstein-Barr virus (EBV) quantification is a crucial prognostic indicator in NPC cases, but not all patients with NPC test positive for EBV. Furthermore, widespread adoption of EBV-DNA quantification remains challenging due to its high cost. Consequently, it is imperative to incorporate additional convenient and cost-effective prognostic markers to comprehensively evaluate patient outcomes. METHODS: This retrospective analysis included 203 newly diagnosed NPC cases treated at the Affiliated Qingyuan Hospital of Guangzhou Medical University between January 2018 and March 2022. The dataset included personal information and clinical data, and the treatment protocols followed the CSCO guidelines. Efficacy assessments were based on the RECIST 1.1 criteria and were conducted after induction chemotherapy and one week and three months after radiotherapy. RESULTS: A noteworthy correlation emerged between baseline serum LDH levels and treatment efficacy at one week after radiotherapy (P = 0.03) and at three months after radiotherapy (P < 0.01). Additionally, a prognostic model that incorporates age (P = 0.010), LDH (P < 0.001), C-reactive protein (P = 0.010), and alkaline phosphatase (P = 0.005) demonstrated robust predictive accuracy and clinical applicability. CONCLUSION: This investigation substantiates the significant correlation between baseline serum LDH levels and NPC outcomes. Furthermore, we introduce a refined prognostic model that holds promise for informing personalized treatment strategies, thereby contributing to the advancement of the diagnosis of NPC.
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L-Lactato Deshidrogenasa , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Humanos , Femenino , Masculino , Carcinoma Nasofaríngeo/sangre , Carcinoma Nasofaríngeo/tratamiento farmacológico , Carcinoma Nasofaríngeo/patología , L-Lactato Deshidrogenasa/sangre , Persona de Mediana Edad , Estudios Retrospectivos , Neoplasias Nasofaríngeas/sangre , Neoplasias Nasofaríngeas/virología , Neoplasias Nasofaríngeas/diagnóstico , Neoplasias Nasofaríngeas/tratamiento farmacológico , Pronóstico , Adulto , Anciano , Biomarcadores de Tumor/sangre , Herpesvirus Humano 4/aislamiento & purificación , Resultado del Tratamiento , Adulto Joven , Análisis Multivariante , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/sangre , Relevancia ClínicaRESUMEN
BACKGROUND: Despite evidence supporting the high correlation of the novel platelet-to-albumin ratio (PAR) with survival in diverse malignancies, its prognostic relevance in nasopharyngeal carcinoma (NPC) remains underexplored. This study aimed to examine the link between PAR and overall survival (OS) in NPC and to establish a predictive model based on this biomarker. METHODS: We retrospectively assembled a cohort consisting of 858 NPC patients who underwent concurrent chemoradiotherapy (CCRT). Utilizing the maximally selected log-rank method, we ascertained the optimal cut-off point for the PAR. Subsequently, univariate and multivariate Cox proportional hazards models were employed to discern factors significantly associated with OS and to construct a predictive nomogram. Further, we subjected the nomogram's predictive accuracy to rigorous independent validation. RESULTS: The discriminative optimal PAR threshold was determined to be 4.47, effectively stratifying NPC patients into two prognostically distinct subgroups (hazard ratio [HR] = 0.53; 95% confidence interval [CI]: 0.28-0.98, P = 0.042). A predictive nomogram was formulated using the results from multivariate analysis, which revealed age greater than 45 years, T stage, N stage, and PAR score as independent predictors of OS. The nomogram demonstrated a commendable predictive capability for OS, with a C-index of 0.69 (95% CI: 0.64-0.75), surpassing the performance of the conventional staging system, which had a C-index of 0.56 (95% CI: 0.65-0.74). CONCLUSIONS: In the context of NPC patients undergoing CCRT, the novel nutritional-inflammatory biomarker PAR emerges as a promising, cost-efficient, easily accessible, non-invasive, and potentially valuable predictor of prognosis. The predictive efficacy of the nomogram incorporating the PAR score exceeded that of the conventional staging approach, thereby indicating its potential as an enhanced prognostic tool in this clinical setting.
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Quimioradioterapia , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Nomogramas , Humanos , Femenino , Masculino , Estudios Retrospectivos , Persona de Mediana Edad , Carcinoma Nasofaríngeo/terapia , Carcinoma Nasofaríngeo/mortalidad , Carcinoma Nasofaríngeo/sangre , Carcinoma Nasofaríngeo/patología , Quimioradioterapia/métodos , Pronóstico , Neoplasias Nasofaríngeas/terapia , Neoplasias Nasofaríngeas/mortalidad , Neoplasias Nasofaríngeas/sangre , Neoplasias Nasofaríngeas/patología , Adulto , Plaquetas/patología , Anciano , Albúmina Sérica/análisis , Estadificación de Neoplasias , Adulto Joven , Modelos de Riesgos Proporcionales , Recuento de Plaquetas , Biomarcadores de Tumor/sangreRESUMEN
Nasopharyngeal carcinoma (NPC), a malignant cancer originating from the epithelial cells of the nasopharynx, presents diagnostic challenges with current methods such as plasma Epstein-Barr virus (EBV) DNA testing showing limited efficacy. This study focused on identifying small extracellular vesicle (sEV) proteins as potential noninvasive biomarkers to enhance NPC diagnostic accuracy. We isolated sEVs from plasma and utilized 4D label-free proteomics to identify differentially expressed proteins (DEPs) among healthy controls (NC = 10), early-stage NPC (E-NPC = 10), and late-stage NPC (L-NPC = 10). Eighteen sEV proteins were identified as potential biomarkers. Subsequently, parallel reaction monitoring (PRM) proteomic analysis preliminarily confirmed sEV carbonic anhydrase 1 (CA1) as a highly promising biomarker for NPC, particularly in early-stage diagnosis (NC = 15; E-NPC = 10; L-NPC = 15). To facilitate this, we developed an automated, high-throughput and highly sensitive CA1 immune-chemiluminescence chip technology characterized by a broad linear detection range and robust controls. Further validation in an independent retrospective cohort (NC = 89; E-NPC = 39; L-NPC = 172) using this technology confirmed sEV CA1 as a reliable diagnostic biomarker for NPC (AUC = 0.9809) and E-NPC (AUC = 0.9893), independent of EBV-DNA testing. Notably, sEV CA1 exhibited superior diagnostic performance compared to EBV-DNA, with a significant incremental net reclassification improvement of 27.61 % for NPC and 72.11 % for E-NPC detection. Thus, this study identifies sEV CA1 as an innovative diagnostic biomarker for NPC and E-NPC independent of EBV-DNA. Additionally, it establishes an immune-chemiluminescence chip technology for the detection of sEV CA1 protein, paving the way for further validation and clinical application.
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Biomarcadores de Tumor , Vesículas Extracelulares , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo/diagnóstico , Carcinoma Nasofaríngeo/sangre , Carcinoma Nasofaríngeo/virología , Biomarcadores de Tumor/sangre , Vesículas Extracelulares/metabolismo , Masculino , Neoplasias Nasofaríngeas/diagnóstico , Neoplasias Nasofaríngeas/sangre , Neoplasias Nasofaríngeas/virología , Femenino , Persona de Mediana Edad , Adulto , Proteómica/métodos , AncianoRESUMEN
Purpose: This study aims to explore the prognostic values of routine pre-treatment hematological parameters in patients with nasopharyngeal carcinoma (NPC). Methods: The hematological parameters and clinical data of patients with NPC were collected from January 2012 to December 2013 at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology. The survival statistics were obtained by regularly following-up the patients. The cut-off values for the hematological parameters were calculated using X-tile software. SPSS version 24.0 was used for the statistical analysis. The relationship between the hematological parameters and the prognosis of patients with NPC was analyzed using the Kaplan-Meier method and Cox multivariate regression. The discriminating abilities of the factors, which predict the prognosis, were evaluated by utilizing the receiver operating characteristic (ROC) area under the curve (AUC). Results: This study included 179 patients with NPC. Multivariate analysis shows that pretreatment platelet-to-lymphocyte ratio (PLR; hazard ratio; HR = 0.44, 95% CI [0.21-0.91], p = 0.029), serum albumin (ALB; HR = 2.49, 95% CI [1.17-5.30], p = 0.018), and globulin (GLO; HR = 0.44, 95% CI [0.21-0.90], p = 0.024) are independent predictors for 5-year overall survival (OS) in patients with NPC. In addition, pre-treatment PLR (HR = 0.47, 95% CI [0.25-0.90], p = 0.022) and pre-treatment GLO (HR = 0.37, 95% CI [0.19-0.72], p = 0.001) are associated with 5-year progression-free survival (PFS) in patients with NPC. Based on the results of the multivariate analysis, we proposed a new biomarker GLO-PLR, which is observably correlated with the T stage, N stage and clinical stage in patients with NPC. The OS resolving ability of the GLO-PLR evaluated by AUC is 0.714, which is better than those of GLO and PLR. The PFS resolving ability of the GLO-PLR evaluated by AUC was 0.696, which is also better than those of GLO and PLR. Conclusion: Pre-treatment PLR, ALB, and GLO are independent predictors of 5-year OS in patients with NPC, where PLR and GLO are also independent predictors of 5-year FPS. Compared with other hematological parameters, the proposed GLO-PLR is an inexpensive, effective, objective, and easy-to-measure marker for predicting the prognosis of NPC.
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Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Humanos , Masculino , Femenino , Persona de Mediana Edad , Carcinoma Nasofaríngeo/sangre , Carcinoma Nasofaríngeo/mortalidad , Carcinoma Nasofaríngeo/diagnóstico , Carcinoma Nasofaríngeo/patología , Estudios Retrospectivos , Neoplasias Nasofaríngeas/sangre , Neoplasias Nasofaríngeas/mortalidad , Neoplasias Nasofaríngeas/diagnóstico , Neoplasias Nasofaríngeas/patología , Pronóstico , Adulto , Anciano , Albúmina Sérica/análisis , Albúmina Sérica/metabolismo , Recuento de Plaquetas , Curva ROC , Estimación de Kaplan-Meier , Recuento de Linfocitos , Plaquetas/patologíaRESUMEN
Nasopharyngeal carcinoma (NPC) risk prediction models based on Epstein-Barr virus (EBV)-antibody testing have shown potential for screening of NPC; however, the long-term stability is unclear. Here, we investigated the kinetics of two EBV-antibody NPC risk scores within the Taiwan NPC Multiplex Family Study. Among 545 participants with multiple blood samples, we evaluated the stability of a 2-marker enzyme-linked immunosorbent assay score and 13-marker multiplex serology score using the intra-class correlation coefficient (ICC) by fitting a linear mixed model that accounted for the clustering effect of multiple measurements per subject and age. We also estimated the clustering of positive tests using Fleiss's kappa statistic. Over an average 20-year follow-up, the 2-marker score showed high stability over time, whereas the 13-marker score was more variable (p < .05). Case-control status is associated with the kinetics of the antibody response, with higher ICCs among cases. Positive tests were more likely to cluster within the same individual for the 2-marker score than the 13-marker score (p < .05). The 2-marker score had an increase in specificity from ~90% for single measurement to ~96% with repeat testing. The 13-marker score had a specificity of ~73% for a single measurement that increased to ~92% with repeat testing. Among individuals who developed NPC, none experienced score reversion. Our findings suggest that repeated testing could improve the specificity of NPC screening in high-risk NPC multiplex families. Further studies are required to determine the impact on sensitivity, establish optimal screening intervals, and generalize these findings to general population settings in high-risk regions.
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Anticuerpos Antivirales , Infecciones por Virus de Epstein-Barr , Herpesvirus Humano 4 , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Humanos , Taiwán/epidemiología , Herpesvirus Humano 4/inmunología , Anticuerpos Antivirales/sangre , Masculino , Femenino , Infecciones por Virus de Epstein-Barr/inmunología , Infecciones por Virus de Epstein-Barr/epidemiología , Infecciones por Virus de Epstein-Barr/virología , Adulto , Persona de Mediana Edad , Neoplasias Nasofaríngeas/virología , Neoplasias Nasofaríngeas/inmunología , Neoplasias Nasofaríngeas/diagnóstico , Neoplasias Nasofaríngeas/sangre , Neoplasias Nasofaríngeas/epidemiología , Carcinoma Nasofaríngeo/virología , Carcinoma Nasofaríngeo/inmunología , Carcinoma Nasofaríngeo/diagnóstico , Carcinoma Nasofaríngeo/sangre , Carcinoma Nasofaríngeo/epidemiología , Cinética , Estudios de Casos y Controles , Ensayo de Inmunoadsorción Enzimática , Adulto Joven , Factores de Riesgo , AncianoRESUMEN
BACKGROUND: This study aims to investigate the predictive value of the circulating blood cell count, including neutro-philto-lymphocyte ratio (NLR), platelet-to-lymphocyte (PLR), and thesystemic inflammation index (SII) for the development of severe oral mucositis (SOM) induced by radiation in patients undergoing radiotherapy for nasopharyngeal carcinoma (NPC). METHODS: In this retrospective study, 142 NPC patients were screened, and based on mucositis toxicity grade, they were categorized into two groups: SOM and nonSOM. Peripheral blood cell counts were conducted prior to Intensity-Modulated Radiation Therapy (IMRT). Associations between blood cell count, NLR, PLR, SII, and SOM occurrence were examined. RESULTS: Revealed elevated NLR and SII levels, along with reduced lymphocyte (LYM), eosinophil (EOS), and basophil (BAS) in patients with SOM. LYM, EOS, BAS, NLR, and SII were effective predictors of the severity of radiation-induced oral mucositis (RIOM) in NPC patients. CONCLUSIONS: The occurrence of SOM was strongly linked to the hematological status at the start of Radiation Therapy (RT). Integrating BAS count and NLR into comprehensive risk prediction models could prove valuable for predicting SOM in NPC patients.
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Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Radioterapia de Intensidad Modulada , Estomatitis , Humanos , Estudios Retrospectivos , Masculino , Femenino , Radioterapia de Intensidad Modulada/efectos adversos , Persona de Mediana Edad , Estomatitis/etiología , Estomatitis/sangre , Estomatitis/patología , Carcinoma Nasofaríngeo/radioterapia , Carcinoma Nasofaríngeo/sangre , Carcinoma Nasofaríngeo/patología , Adulto , Neoplasias Nasofaríngeas/radioterapia , Neoplasias Nasofaríngeas/sangre , Anciano , Pronóstico , Traumatismos por Radiación/sangre , Traumatismos por Radiación/etiología , Traumatismos por Radiación/patología , Traumatismos por Radiación/diagnóstico , Biomarcadores/sangre , Inflamación/etiología , Inflamación/sangre , Estudios de Seguimiento , Valor Predictivo de las PruebasRESUMEN
BACKGROUND: Long non-coding RNAs (lncRNAs) in serum were useful and promising biomarkers for diagnostic and prognostic application. Herein, we investigated the serum lncRNA LINC00339 expression and its role in nasopharyngeal carcinoma. METHODS: In this study, we recruited a cohort of 129 nasopharyngeal carcinoma patients, 68 patients with nasopharyngitis, and 80 healthy controls. Serum LINC00339 levels were measured by reverse transcription-quantitative polymerase chain reaction. Receiver operating characteristic (ROC) and Kaplan-Meier curve analyses were conducted to evaluate th e clinical role of LINC00339. The effects of linc00339 on cellular activities were measured using CCK-8 and Transwell assays. RESULTS: We observed that serum LINC00339 expression was upregulated in nasopharyngeal carcinoma patients and closely associated with tumor node metastasis stage, lymph node metastasis, and overall survival rate. Meanwhile, ROC analysis showed serum LINC00339 had diagnostic value to distinguish nasopharyngeal carcinoma patients from healthy individuals and nasopharyngitis patients. Silencing of LINC00339 could repress cellular behaviors by targeting miR-152. CONCLUSION: This study clarified that LINC00339 was upregulated in nasopharyngeal carcinoma, and that serum LINC00339 may act as a diagnostic or prognostic marker, and a hopeful therapeutic target for patients with nasopharyngeal carcinoma.
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Biomarcadores de Tumor , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , ARN Largo no Codificante , Humanos , ARN Largo no Codificante/sangre , ARN Largo no Codificante/genética , Carcinoma Nasofaríngeo/sangre , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/patología , Femenino , Masculino , Biomarcadores de Tumor/sangre , Biomarcadores de Tumor/genética , Pronóstico , Persona de Mediana Edad , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/sangre , Neoplasias Nasofaríngeas/patología , Adulto , MicroARNs/sangre , MicroARNs/genética , Regulación Neoplásica de la Expresión GénicaRESUMEN
BACKGROUND: Advancements in nasopharyngeal carcinoma (NPC) treatment have led to a focus on personalized treatment. Circulating tumor cells (CTCs) are important for liquid biopsies and personalized treatment but are not being fully utilized. This study examined how pre- and post-treatment CTC counts, EMT subtypes, clinical characteristics, and patient prognosis are related in order to support the use of liquid biopsy in managing NPC. METHODS: This retrospective study included 141 patients with locally advanced NPC. All patients underwent CanPatrol™ CTC detection pre- and post-treatment and were categorized into EMT subtypes: epithelial type, mixed type, and mesenchymal type. This study analyzed CTC enumeration, EMT subtypes, and their associations with clinical characteristics and survival outcomes. RESULTS: The results indicated a positive correlation between the pre-treatment detection rate of CTCs and N stage (P < 0.01), alongside a positive correlation with the TNM clinical stage (P = 0.02). Additionally, the detection rate of mesenchymal CTCs post-treatment is positively associated with the N stage (P = 0.02). The enumeration of CTCs pre- and post-treatment is negatively correlated with prognosis and has statistical significance. Additionally, an investigation into the EMT subtypes of CTCs revealed a significant association between the presence of mesenchymal CTCs pre- and post-treatment and decreased overall survival (OS) (P < 0.05). Furthermore, T stage, N stage, TNM clinical stage, and Epstein-Barr virus (EBV) DNA were also significantly correlated with OS. CONCLUSION: The study found that mesenchymal CTCs pre- and post-treatment, as well as the number of CTCs, were linked to a poor prognosis.
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Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Estadificación de Neoplasias , Células Neoplásicas Circulantes , Humanos , Células Neoplásicas Circulantes/patología , Masculino , Femenino , Estudios Retrospectivos , Carcinoma Nasofaríngeo/patología , Carcinoma Nasofaríngeo/mortalidad , Carcinoma Nasofaríngeo/sangre , Carcinoma Nasofaríngeo/terapia , Persona de Mediana Edad , Neoplasias Nasofaríngeas/patología , Neoplasias Nasofaríngeas/mortalidad , Neoplasias Nasofaríngeas/terapia , Neoplasias Nasofaríngeas/sangre , Neoplasias Nasofaríngeas/diagnóstico , Adulto , Pronóstico , Anciano , Transición Epitelial-Mesenquimal , Biopsia Líquida/métodosRESUMEN
BACKGROUND: Liquid biopsy, including the detection of circulating tumor cells (CTCs), has emerged as a promising tool for cancer diagnosis and monitoring. However, the prognostic value of CTCs in nasopharyngeal carcinoma (NPC) remains unclear due to the lack of phenotypic characterization. The expression of Excision Repair Cross-Complementation Group 1 (ERCC1) and CTCs epithelial-mesenchymal transition (EMT) have been associated with treatment efficacy. In this study, we aimed to evaluate the prognostic significance of ERCC1 expression on CTCs and their EMT subtypes before treatment in NPC. METHODS: We retrospectively analyzed 108 newly diagnosed locally advanced NPC patients who underwent CanPatrol™ CTC testing between November 2018 and November 2021. CTCs were counted and classified into epithelial, epithelial-mesenchymal hybrid, and mesenchymal subtypes. ERCC1 expression was divided into negative and positive groups. Clinical features and survival outcomes were analyzed. RESULTS: The positive rate of CTCs was 92.6% (100/108), with an ERCC1 positivity rate of 74% (74/100). Further analysis of the subtypes showed that positive ERCC1 on mesenchymal CTCs was associated with a later N stage (P = .01). Positive ERCC1 expression was associated with poor overall survival (OS; P = .039) and disease-free survival (DFS; P = .035). Further analysis of subtypes showed that the positive ERCC1 on mesenchymal-type CTCs was associated with poor OS (P = .012) and metastasis-free survival (MFS; P = .001). CONCLUSION: Our findings suggest that ERCC1 expression on CTCs may serve as a new prognostic marker for NPC patients. Evaluating CTCs subtypes may become an auxiliary tool for personalized and precise treatment.
BackgroundLiquid biopsy, including the detection of circulating tumor cells (CTCs), has emerged as a promising tool for cancer diagnosis and monitoring. However, the prognostic value of CTCs in nasopharyngeal carcinoma (NPC) remains unclear due to the lack of phenotypic characterization. The expression of Excision Repair Cross-Complementation Group 1 (ERCC1) and CTCs epithelial-mesenchymal transition (EMT) have been associated with treatment efficacy. In this study, we aimed to evaluate the prognostic significance of ERCC1 expression on CTCs and their EMT subtypes before treatment in NPC.MethodsWe retrospectively analyzed 108 newly diagnosed locally advanced NPC patients who underwent CanPatrol™ CTC testing between November 2018 and November 2021. CTCs were counted and classified into epithelial, epithelial-mesenchymal hybrid, and mesenchymal subtypes. ERCC1 expression was divided into negative and positive groups. Clinical features and survival outcomes were analyzed.ResultsThe positive rate of CTCs was 92.6% (100/108), with an ERCC1 positivity rate of 74% (74/100). Further analysis of the subtypes showed that positive ERCC1 on mesenchymal CTCs was associated with a later N stage (P = .01). Positive ERCC1 expression was associated with poor overall survival (OS; P = .039) and disease-free survival (DFS; P = .035). Further analysis of subtypes showed that the positive ERCC1 on mesenchymal-type CTCs was associated with poor OS (P = .012) and metastasis-free survival (MFS; P = .001).ConclusionOur findings suggest that ERCC1 expression on CTCs may serve as a new prognostic marker for NPC patients. Evaluating CTCs subtypes may become an auxiliary tool for personalized and precise treatment.
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Proteínas de Unión al ADN , Endonucleasas , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Células Neoplásicas Circulantes , Humanos , Células Neoplásicas Circulantes/metabolismo , Células Neoplásicas Circulantes/patología , Carcinoma Nasofaríngeo/patología , Carcinoma Nasofaríngeo/sangre , Carcinoma Nasofaríngeo/mortalidad , Carcinoma Nasofaríngeo/metabolismo , Masculino , Femenino , Pronóstico , Persona de Mediana Edad , Endonucleasas/metabolismo , Estudios Retrospectivos , Neoplasias Nasofaríngeas/patología , Neoplasias Nasofaríngeas/sangre , Neoplasias Nasofaríngeas/mortalidad , Proteínas de Unión al ADN/metabolismo , Transición Epitelial-Mesenquimal/genética , Adulto , Biomarcadores de Tumor/metabolismo , Anciano , Reparación por EscisiónRESUMEN
Objective: This study aimed to establish an effective prognostic model based on triglyceride and inflammatory markers, including neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and platelet-to-lymphocyte ratio (PLR), to predict overall survival (OS) in patients with nasopharyngeal carcinoma (NPC). Additionally, we aimed to explore the interaction and mediation between these biomarkers in their association with OS. Methods: A retrospective review was conducted on 259 NPC patients who had blood lipid markers, including triglyceride and total cholesterol, as well as parameters of peripheral blood cells measured before treatment. These patients were followed up for over 5 years, and randomly divided into a training set (n=155) and a validation set (n=104). The triglyceride-inflammation (TI) score was developed using the random survival forest (RSF) algorithm. Subsequently, a nomogram was created. The performance of the prognostic model was measured by the concordance index (C-index), time-dependent receiver operating characteristic (ROC) curve, and decision curve analysis (DCA). The interaction and mediation between the biomarkers were further analyzed. Bioinformatics analysis based on the GEO dataset was used to investigate the association between triglyceride metabolism and immune cell infiltration. Results: The C-index of the TI score was 0.806 in the training set, 0.759 in the validation set, and 0.808 in the entire set. The area under the curve of time-dependent ROC of TI score in predicting survival at 1, 3, and 5 years were 0.741, 0.847, and 0.871 respectively in the training set, and 0.811, 0.837, and 0.758 in the validation set, then 0.771, 0.848, and 0.862 in the entire set, suggesting that TI score had excellent performance in predicting OS in NPC patients. Patients with stage T1-T2 or M0 had significantly lower TI scores, NLR, and PLR, and higher LMR compared to those with stage T3-T3 or M1, respectively. The nomogram, which integrated age, sex, clinical stage, and TI score, demonstrated good clinical usefulness and predictive ability, as evaluated by the DCA. Significant interactions were found between triglyceride and NLR and platelet, but triglyceride did not exhibit any medicating effects in the inflammatory markers. Additionally, NPC tissues with active triglyceride synthesis exhibited high immune cell infiltration. Conclusion: The TI score based on RSF represents a potential prognostic factor for NPC patients, offering convenience and economic advantages. The interaction between triglyceride and NLR may be attributed to the effect of triglyceride metabolism on immune response.