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BACKGROUND: N6-methyladenosine (m6A) and 5-methylcytosine (m5C) play a role in modifying long non-coding RNAs (lncRNAs) implicated in tumorigenesis and progression. This study was performed to evaluate prognostic value of m6A- and m5C-related lncRNAs and develop an efficient model for prognosis prediction in cervical cancer (CC). METHODS: Using gene expression data of TCGA set, we identified m6A- and m5C-related lncRNAs. Consensus Clustering Analysis was performed for samples subtyping based on survival-related lncRNAs, followed by analyzing tumor infiltrating immune cells (TIICs). Optimal signature lncRNAs were obtained using lasso Cox regression analysis for constructing a prognostic model and a nomogram to predict prognosis. RESULTS: We built a co-expression network of 23 m6A-related genes, 15 m5C-related genes, and 62 lncRNAs. Based on 9 m6A- and m5C-related lncRNAs significantly associated with overall survival (OS) time, two molecular subtypes were obtained, which had significantly different OS time and fractions of TIICs. A prognostic model based on six m6A- and m5C-related signature lncRNAs was constructed, which could dichotomize patients into two risk subgroups with significantly different OS time. Prognostic power of the model was successfully validated in an independent dataset. We subsequently constructed a nomogram which could accurately predict survival probabilities. Drug sensitivity analysis found preferred chemotherapeutic agents for high and low-risk patients, respectively. CONCLUSION: Our study reveals that m6A- and m5C-related lncRNAs are associated with prognosis and immune microenvironment of CC. The m6A- and m5C-related six-lncRNA signature may be a useful tool for survival stratification in CC and open new avenues for individualized therapies.

Asunto(s)

5-Metilcitosina , Adenosina , ARN Largo no Codificante , Neoplasias del Cuello Uterino , ARN Largo no Codificante/genética , Humanos , Adenosina/análogos & derivados , Adenosina/genética , Adenosina/metabolismo , Neoplasias del Cuello Uterino/genética , Neoplasias del Cuello Uterino/mortalidad , Neoplasias del Cuello Uterino/diagnóstico , Femenino , 5-Metilcitosina/análogos & derivados , 5-Metilcitosina/metabolismo , Pronóstico , Regulación Neoplásica de la Expresión Génica , Nomogramas , Biomarcadores de Tumor/genética , Perfilación de la Expresión Génica

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BACKGROUND: As assessment tools of nutritional status, the controlling nutritional status (CONUT) and modified controlling nutritional status (mCONUT) score are associated with survival in various cancers. We aimed to investigate the association between the CONUT/mCONUT score's prognostic value and survival time in patients with FIGO stage IIB-IIIB cervical cancer treated with radiotherapy. METHODS: In this retrospective study, 165 patients between September 2013 and September 2015 were analyzed, and the optimal CONUT/mCONUT score cut-off values were determined using receiver operating characteristic curves. Propensity score matching (PSM) was used to minimize selection bias. The Kaplan-Meier method and a Cox proportional hazard model were used to assess the CONUT/mCONUT score's predictive value linked to survival time. Two nomograms were created to predict the overall survival (OS) and progression-free survival (PFS). RESULTS: The cut-off values for CONUT and mCONUT score were both 2. Five-year OS and PFS rates were higher in a low CONUT score group than in a high CONUT score group (OS: 81.1% vs. 53.8%, respectively, P < 0.001; PFS: 76.4% vs. 48.2%, respectively; P < 0.001). A high CONUT score was associated with decreased OS (hazard ratio (HR) 2.93, 95% CI 1.54-5.56; P = 0.001) and PFS (HR 2.77, 95% CI 1.52-5.04; P < 0.001). High CONUT scores influenced OS in the PSM cohort. A high mCONUT score was not associated with decreased OS and PFS in Cox regression analysis. CONCLUSION: The CONUT score is a promising indicator for predicting survival in patients with cervical cancer receiving radiotherapy.

Asunto(s)

Estado Nutricional , Puntaje de Propensión , Neoplasias del Cuello Uterino , Humanos , Neoplasias del Cuello Uterino/radioterapia , Neoplasias del Cuello Uterino/mortalidad , Neoplasias del Cuello Uterino/patología , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Pronóstico , Adulto , Anciano , Estimación de Kaplan-Meier , Nomogramas , Estadificación de Neoplasias , Evaluación Nutricional , Curva ROC , Modelos de Riesgos Proporcionales

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BACKGROUND: Cervical cancer, encompassing squamous cell carcinoma and endocervical adenocarcinoma (CESC), presents a considerable risk to the well-being of women. Recent studies have reported that squalene epoxidase (SQLE) is overexpressed in several cancers, which contributes to cancer development. METHODS: RNA sequencing data for SQLE were obtained from The Cancer Genome Atlas. In vitro experiments, including colorimetry, colony formation, Transwell, RT-qPCR, and Western blotting were performed. Furthermore, a transplanted CESC nude mouse model was constructed to validate the tumorigenic activity of SQLE in vivo. Associations among the SQLE expression profiles, differentially expressed genes (DEGs), immune infiltration, and chemosensitivity were examined. The prognostic value of genetic changes and DNA methylation in SQLE were also assessed. RESULTS: SQLE mRNA expression was significantly increased in CESC. ROC analysis revealed the strong diagnostic ability of SQLE toward CESC. Patients with high SQLE expression experienced shorter overall survival. The promotional effects of SQLE on cancer cell proliferation, metastasis, cholesterol synthesis, and EMT were emphasized. DEGs functional enrichment analysis revealed the signaling pathways and biological processes. Notably, a connection existed between the SQLE expression and the presence of immune cells as well as the activation of immune checkpoints. Increased SQLE expressions exhibited increased chemotherapeutic responses. SQLE methylation status was significantly associated with CESC prognosis. CONCLUSION: SQLE significantly affects CESC prognosis, malignant behavior, cholesterol synthesis, EMT, and immune infiltration; thereby offering diagnostic and indicator roles in CESC. Thus, SQLE can be a novel therapeutic target in CESC treatment.

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Biomarcadores de Tumor , Colesterol , Transición Epitelial-Mesenquimal , Escualeno-Monooxigenasa , Neoplasias del Cuello Uterino , Humanos , Neoplasias del Cuello Uterino/genética , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/inmunología , Neoplasias del Cuello Uterino/mortalidad , Femenino , Transición Epitelial-Mesenquimal/genética , Animales , Pronóstico , Escualeno-Monooxigenasa/genética , Escualeno-Monooxigenasa/metabolismo , Ratones , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Colesterol/metabolismo , Ratones Desnudos , Regulación Neoplásica de la Expresión Génica , Metilación de ADN , Línea Celular Tumoral , Proliferación Celular , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/inmunología , Adenocarcinoma/genética , Adenocarcinoma/patología , Adenocarcinoma/inmunología , Linfocitos Infiltrantes de Tumor/inmunología , Linfocitos Infiltrantes de Tumor/metabolismo

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Despite improvements in vaccination, screening, and treatment, cervical cancer (CC) remains a major healthcare problem on a global scale. The tumor microenvironment (TME) plays an important and controversial role in cancer development, and the mechanism of the tumor's escape from immunological surveillance is still not clearly defined. We aim to investigate the expression of CD68 and CD47 in patients with different histological variants of CC, tumor characteristics, and burden. This is a retrospective cohort study performed on paraffin-embedded tumor tissues from 191 patients diagnosed with CC between 2014 and 2021 at the Medical University Pleven, Bulgaria. Slides for immunohistochemical (IHC) evaluation were obtained, and the expression of CD68 was scored in intratumoral (IT) and stromal (ST) macrophages (CD68+cells) using a three-point scoring scale. The CD47 expression was reported as an H-score. All statistical analyses were performed using R v. 4.3.1 for Windows. Infiltration by CD68-IT cells in the tumor depended on histological type and the expression of CD47. Higher levels of the CD47 H-score were significantly more frequent among patients in the early stage. Higher levels of infiltration by CD68-ST cells were associated with worse prognosis, and the infiltration of CD68-IT cells was associated with reduced risk of death from neoplastic disease. TME is a complex ecosystem that has a major role in the growth and development of tumors. Macrophages are a major component of innate immunity and, when associated with a tumor process, are defined as TAM. Tumor cells try to escape immunological surveillance in three ways, and one of them is reducing immunogenicity by the overexpression of negative coreceptors by T-lymphocytes and their ligands on the surface of tumor cells. One such mechanism is the expression of CD47 in tumor cells, which sends a "don't eat me" signal to the macrophages and, thus, prevents phagocytosis. To our knowledge, this is the first study that has tried to establish the relationship between the CD47 and CD68 expression levels and some clinicopathologic features in CC. We found that the only clinicopathological feature implicating the level of CD68 infiltration was the histological variant of the tumor, and only for CD68-IT-high levels were these observed in SCC. High levels of CD47 expression were seen more frequently in pT1B than pT2A and pT2B in the FIGO I stage than in the FIGO II and III stages. Infiltration by large numbers of CD68-IT cells was much more common among patients with a high expression of CD47 in tumor cells. A high level of infiltration by CD68-ST cells was associated with a worse prognosis, and a high level of infiltration by CD68-ST cells was associated with a lower risk of death from cancer.

Asunto(s)

Antígenos CD , Antígenos de Diferenciación Mielomonocítica , Biomarcadores de Tumor , Antígeno CD47 , Microambiente Tumoral , Neoplasias del Cuello Uterino , Humanos , Neoplasias del Cuello Uterino/inmunología , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/metabolismo , Neoplasias del Cuello Uterino/mortalidad , Femenino , Antígeno CD47/metabolismo , Pronóstico , Microambiente Tumoral/inmunología , Antígenos de Diferenciación Mielomonocítica/metabolismo , Persona de Mediana Edad , Biomarcadores de Tumor/metabolismo , Antígenos CD/metabolismo , Estudios Retrospectivos , Adulto , Anciano , Macrófagos/metabolismo , Macrófagos/inmunología , Fagocitosis , Macrófagos Asociados a Tumores/metabolismo , Macrófagos Asociados a Tumores/inmunología , Molécula CD68

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BACKGROUND: The prognostic value of the pretreatment prognostic nutritional index (PNI) for gynaecological malignancies remain unclear. This meta-analysis aimed to explore the predictive significance of the PNI for gynaecological tumours. METHODS: The PubMed, Embase, Web of Science, and Cochrane Library databases were searched up to January 30, 2024, to identify relevant studies. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to assess the associations of the PNI with overall survival (OS), progression-free survival (PFS), and disease-free survival (DFS) in patients with gynaecological tumours. We examined the correlation of the PNI with clinicopathological parameters of patients with gynaecological carcinoma by utilizing pooled odds ratios (ORs) and 95% CIs. RESULTS: A total of 28 articles involving 9,428 patients were included in the meta-analysis. The results revealed that a low PNI significantly predicted worse OS (HR = 1.60, 95% CI: 1.39-1.84, P < 0.001), PFS (HR = 1.63, 95% CI: 1.20-2.23, P = 0.002), and DFS (HR = 1.73, 95% CI: 1.19-2.52, P = 0.004). In addition, the subgroup analysis confirmed that the PNI had a prognostic effect on OS for all cancer types, but a significant association with PFS was not observed in patients with cervical cancer. A low PNI was significantly associated with FIGO stages III‒IV (OR = 2.30, 95% CI: 1.89‒2.80, P < 0.001) and LN metastasis (OR = 2.76, 95% CI: 2. 05‒3.73, P < 0.001). CONCLUSION: The PNI may be noninvasive and promising biomarker for predicting the prognosis of patients with gynaecological tumours.

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Neoplasias Endometriales , Evaluación Nutricional , Neoplasias Ováricas , Neoplasias del Cuello Uterino , Humanos , Femenino , Pronóstico , Neoplasias Endometriales/mortalidad , Neoplasias Endometriales/patología , Neoplasias Endometriales/diagnóstico , Neoplasias Ováricas/mortalidad , Neoplasias Ováricas/patología , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/mortalidad , Neoplasias del Cuello Uterino/diagnóstico , Supervivencia sin Enfermedad

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Cervical cancer is one of the most dangerous malignancies in women. Prolonged survival times are made possible by breakthroughs in early recognition and efficient treatment of a disease.The existing methods are lagging on finding the important attributes to predict the survival outcome. The main objective of this study is to find individuals with cervical cancer who are at greater risk of death from recurrence by predicting the survival.A novel approach in a proposed technique is Triangulating feature importance to find the important risk factors through which the treatment may vary to improve the survival outcome.Five algorithms Support vector machine, Naive Bayes, supervised logistic regression, decision tree algorithm, Gradient boosting, and random forest are used to build the concept. Conventional attribute selection methods like information gain (IG), FCBF, and ReliefFare employed. The recommended classifier is evaluated for Precision, Recall, F1, Mathews Correlation Coefficient (MCC), Classification Accuracy (CA), and Area under curve (AUC) using various methods. Gradient boosting algorithm (CAT BOOST) attains the highest accuracy value of 0.99 to predict survival outcome of recurrence cervical cancer patients. The proposed outcome of the research is to identify the important risk factors through which the survival outcome of the patients improved.

Asunto(s)

Algoritmos , Recurrencia Local de Neoplasia , Neoplasias del Cuello Uterino , Neoplasias del Cuello Uterino/mortalidad , Neoplasias del Cuello Uterino/terapia , Neoplasias del Cuello Uterino/patología , Humanos , Femenino , Máquina de Vectores de Soporte , Pronóstico , Factores de Riesgo , Teorema de Bayes , Árboles de Decisión , Análisis de Supervivencia

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PURPOSE: To analyze the survival outcomes of female patients with cervical, uterine, and ovarian cancers in Southeast China (Fujian Province) from 2011 to 2020 and to provide a reference basis for prognostic evaluation and prevention of gynecological malignancies. METHODS: The data of 5823 patients with cervical, uterine, and ovarian cancers registered in the Fujian Provincial Cancer Prevention and Control System from 2011 to 2020 were enrolled for survival analysis and further stratified by age at diagnosis and township. Survival time was calculated up to March 30, 2022, and relative survival (RS) and age-standardized RS were calculated according to the International Cancer Survival Standards (ICSS). RESULTS: During 2011-2015, the 5-year RS for cervical, uterine, and ovarian cancers were 64.3 %, 64.2 %, and 44.7 %, respectively, while the age-standardized 5-year RS were 56.8 %, 47.9 %, and 27.9 %, respectively. During 2016-2020, the 5-year RS for cervical, uterine, and ovarian cancers were 72.3 %, 78.9 %, and 50.8 %, respectively, while the age-standardized 5-year RS were 64.5 %, 54.6 %, and 34.2 %, respectively. The 5-year RS for cervical and ovarian cancer all declined with age, while the 5-year RS for uterine cancer was highest at 45-54 years and lowest at 75 years. In addition, survival rates were broadly higher in urban than rural areas. CONCLUSION: Survival rates for cervical, uterine, and ovarian cancers have generally increased in the population covered by the Fujian Cancer Registry. However, survival rates remain lower than in developed countries. Emphasis should be placed on gynecological cancer screening and the introduction of effective treatments to improve survival rates for gynecological cancers.

Asunto(s)

Neoplasias de los Genitales Femeninos , Humanos , Femenino , China/epidemiología , Persona de Mediana Edad , Adulto , Anciano , Neoplasias de los Genitales Femeninos/mortalidad , Neoplasias de los Genitales Femeninos/epidemiología , Tasa de Supervivencia , Análisis de Supervivencia , Adulto Joven , Sistema de Registros/estadística & datos numéricos , Neoplasias del Cuello Uterino/mortalidad , Neoplasias del Cuello Uterino/epidemiología , Neoplasias del Cuello Uterino/patología , Neoplasias Ováricas/mortalidad , Neoplasias Ováricas/epidemiología , Pronóstico , Adolescente

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PURPOSE: Neuroendocrine carcinoma of the cervix (NECC) is rare but results in poor prognosis. The causes of death (CODs) in NECC patients are rarely reported. Our study aimed to explore the distributions of death causes of NECC patients compared with squamous cell carcinoma (SCC) and adenocarcinoma (ADC) and to develop a validated survival prediction model. METHODS: Patients diagnosed with NECC, SCC, or ADC were identified from the Surveillance, Epidemiology, and End Results Program database from 1975 to 2019. We analyzed the standardized mortality ratio (SMR) to determine each cause of death for each survival time category. The Kaplan-Meier method was used for survival analysis. Univariate and multivariate Cox regression analyses were used to establish a nomogram model. RESULTS: A total of 358 NECC patients were included in this study, and 270 (75.4%) died during the follow-up period. Patients with NECC had 5.55 times (95% CI, 4.53-6.79, p < 0.0001) higher risk of death compared with patients with SCC and 10.38 times (95% CI, 8.28-13.01, p < 0.0001) higher compared with ADC. Cervical cancer is the main cause of death in NECC. As the diagnosis time increased, the risk of death from all causes and cervix cancer gradually decreased. While after at least 10 years of follow-up time, the highest and most dramatical SMR values were observed for metastasis (SMR, 138.81; 95% CI, 37.82-355.40; p < 0.05) and other cancers as the reason for death has an over 7-fold higher SMR (SMR: 7.07; 95% CI: 2.60-15.40, p < 0.05) more than 5 years after the cancer diagnosis. Race, FIGO stage, and surgery were independent risk factors for the overall survival (OS) of NECC patients. For the predictive nomogram, the C-index was 0.711 (95% CI: 0.697-0.725) and was corrected to 0.709 (95% CI: 0.680, 0.737) by bootstrap 1000 resampling validation. CONCLUSION: Compared with SCC and ADC, NECC patients have an elevated risk of mortality due to cervical cancer and metastasis. We successfully constructed a prognostic nomogram for patients with NECC. Based on refractoriness and high mortality of NECC, targeted treatment strategies and follow-up plans should be further developed according to the risk of death and distribution characteristics of CODs.

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Carcinoma Neuroendocrino , Carcinoma de Células Escamosas , Causas de Muerte , Nomogramas , Programa de VERF , Neoplasias del Cuello Uterino , Humanos , Femenino , Carcinoma Neuroendocrino/mortalidad , Carcinoma Neuroendocrino/patología , Neoplasias del Cuello Uterino/mortalidad , Neoplasias del Cuello Uterino/patología , Persona de Mediana Edad , Pronóstico , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/patología , Adulto , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Anciano , Estimación de Kaplan-Meier

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Background: Ferroptosis is a non-apoptotic iron-dependent form of cell death implicated in various cancer pathologies. However, its precise role in tumor growth and progression of cervical cancer (CC) remains unclear. Transferrin receptor protein 1 (TFRC), a key molecule associated with ferroptosis, has been identified as influencing a broad range of pathological processes in different cancers. However, the prognostic significance of TFRC in CC remains unclear. The present study utilized bioinformatics to explore the significance of the ferroptosis-related gene TFRC in the progression and prognosis of CC. Methods: We obtained RNA sequencing data and corresponding clinical information on patients with CC from The Cancer Genome Atlas (TCGA), Genotype Tissue Expression (GTEx) and Gene Expression Omnibus (GEO) databases. Using least absolute shrinkage and selection operator (LASSO) Cox regression, we then generated a multigene signature of five ferroptosis-related genes (FRGs) for the prognostic prediction of CC. We investigated the relationship between TFRC gene expression and immune cell infiltration by employing single-sample GSEA (ssGSEA) analysis. The potential functional role of the TFRC gene was evaluated through gene set enrichment analysis (GSEA). Immunohistochemistry and qPCR was employed to assess TFRC mRNA and protein expression in 33 cases of cervical cancer. Furthermore, the relationship between TFRC mRNA expression and overall survival (OS) was investigated in patients. Results: CC samples had significantly higher TFRC gene expression levels than normal tissue samples. Higher TFRC gene expression levels were strongly associated with higher cancer T stages and OS events. The findings of multivariate analyses illustrated that the OS in CC patients with high TFRC expression is shorter than in patients with low TFRC expression. Significant increases were observed in the levels of TFRC mRNA and protein expression in patients diagnosed with CC. Conclusion: Increased TFRC expression in CC was associated with disease progression, an unfavorable prognosis, and dysregulated immune cell infiltration. In addition, it highlights ferroptosis as a promising therapeutic target for CC.

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Ferroptosis , Receptores de Transferrina , Microambiente Tumoral , Neoplasias del Cuello Uterino , Humanos , Femenino , Ferroptosis/genética , Receptores de Transferrina/genética , Receptores de Transferrina/metabolismo , Neoplasias del Cuello Uterino/genética , Neoplasias del Cuello Uterino/inmunología , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/mortalidad , Microambiente Tumoral/inmunología , Microambiente Tumoral/genética , Pronóstico , Regulación Neoplásica de la Expresión Génica , Antígenos CD/genética , Persona de Mediana Edad , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo

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Gynecological cancer significantly affect the health of women. This review aimed to describe the global patterns and trends in the survival of patients with gynecological cancers. We searched PubMed, Embase, Web of Science, SinoMed, and SEER for survival analyses of cancer registration data of cervical, endometrial, and ovarian cancers published between 1980 and 2022. Globally, the highest 5-year observed survival rate for cervical cancer was 76.5% in Anshan, Liaoning, China (2008-2017). The 5-year observed survival rates of endometrial and ovarian cancers were higher in Finland (1995-1999, 82.5%) and Singapore (1988-1992, 62.0%). The 5-year relative survival rate of cervical cancer patients was higher in Haining, Zhejiang, China (2011-2014, 85.8%). Korea ranked first at 89.0% and 64.5% for endometrial and ovarian cancers, respectively. Survival rates have improved for cervical, endometrial, and ovarian cancers. Patients aged ≥ 75 years and those with advanced-stage disease had the worst 5-year survival rates. Survival rates were better for squamous cell carcinoma in cervical cancer, for endometrial carcinoma and mucinous adenocarcinoma in endometrial cancer, and for germ cell and sex-cord stromal tumors in ovarian cancer. Over the past four decades, the survival rates of gynecological cancers have increased globally, with notable increases in cervical and endometrial cancers. Survival rates are higher in developed countries, with a slow-growing trend. Future studies should focus on improving survival, especially in ovarian cancer patients.

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Neoplasias de los Genitales Femeninos , Humanos , Femenino , Neoplasias de los Genitales Femeninos/mortalidad , Neoplasias de los Genitales Femeninos/epidemiología , Sistema de Registros , Tasa de Supervivencia , Neoplasias del Cuello Uterino/mortalidad , Neoplasias del Cuello Uterino/epidemiología

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Platinum-based neoadjuvant chemotherapy (NACT) followed by radical hysterectomy has been proposed as an alternative treatment approach for cervical cancer (CC) in stage Ib2-IIb, who had a strong desire to be treated with surgery. Our study aims to develop a model based on multimodal MRI by using radiomics and deep learning to predict the treatment response in CC patients treated with neoadjuvant chemoradiotherapy (NACRT). From August 2009 to June 2013, CC patients in stage Ib2-IIb (FIGO 2008) who received NACRT at Fujian Cancer Hospital were enrolled in our study. Clinical information, contrast-enhanced T1-weighted imaging (CE-T1WI), and T2-weighted imaging (T2WI) data were respectively collected. Radiomic features and deep abstract features were extracted from the images using radiomics and deep learning models, respectively. Then, ElasticNet and SVM-RFE were employed for feature selection to construct four single-sequence feature sets. Early fusion of two multi-sequence feature sets and one hybrid feature set were performed, followed by classification prediction using four machine learning classifiers. Subsequently, the performance of the models in predicting the response to NACRT was evaluated by separating patients into training and validation sets. Additionally, overall survival (OS) and disease-free survival (DFS) were assessed using Kaplan-Meier survival curves. Among the four machine learning models, SVM exhibited the best predictive performance (AUC=0.86). Among the seven feature sets, the hybrid feature set achieved the highest values for AUC (0.86), ACC (0.75), Recall (0.75), Precision (0.81), and F1-score (0.75) in the validation set, outperforming other feature sets. Furthermore, the predicted outcomes of the model were closely associated with patient OS and DFS (p = 0.0044; p = 0.0039). A model based on MRI images with features from multiple sequences and different methods could precisely predict the response to NACRT in CC patients. This model could assist clinicians in devising personalized treatment plans and predicting patient survival outcomes.

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Quimioradioterapia , Imagen por Resonancia Magnética , Terapia Neoadyuvante , Neoplasias del Cuello Uterino , Humanos , Femenino , Neoplasias del Cuello Uterino/diagnóstico por imagen , Neoplasias del Cuello Uterino/terapia , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/mortalidad , Terapia Neoadyuvante/métodos , Imagen por Resonancia Magnética/métodos , Persona de Mediana Edad , Adulto , Quimioradioterapia/métodos , Aprendizaje Profundo , Resultado del Tratamiento , Anciano , Imagen Multimodal/métodos , Radiómica

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BACKGROUND: The study aimed to assess the efficacy and safety of 125I seed implantation in the treatment of pelvic recurrent cervical cancer following radiotherapy. This meta-analysis was registered in PROSPERO. We looked up relevant studies in the databases of CNKI, Wanfang, CBM, PubMed, Embase, Cochrane Library, and Web of Science. The endpoint measures include the objective response rate, disease control rate, progression-free survival, overall survival, and adverse events. RECENT FIDINGS: The meta-analysis included six studies and a total of 246 patients. The pooled ORR of tumor response was 63%, and the DCR was 87%. The median PFS was 9.09 months, and the median OS was 13.46 months. The incidence of adverse events of Grade ≥III was 6%. CONCLUSION: In conclusion, this meta-analysis confirmed that 125I seed implantation has a good local control rate and high safety in the treatment of pelvic recurrent cervical cancer following radiotherapy, and can be used as a remedial treatment for pelvic recurrent cervical cancer following radiotherapy to prolong the survival time of patients. TRIAL REGISTRATION: PROSPERO: CRD42023423857.

Asunto(s)

Braquiterapia , Radioisótopos de Yodo , Recurrencia Local de Neoplasia , Neoplasias del Cuello Uterino , Humanos , Neoplasias del Cuello Uterino/radioterapia , Neoplasias del Cuello Uterino/mortalidad , Neoplasias del Cuello Uterino/patología , Radioisótopos de Yodo/uso terapéutico , Radioisótopos de Yodo/efectos adversos , Radioisótopos de Yodo/administración & dosificación , Femenino , Recurrencia Local de Neoplasia/radioterapia , Braquiterapia/efectos adversos , Braquiterapia/métodos , China/epidemiología , Neoplasias Pélvicas/radioterapia , Pueblos del Este de Asia

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OBJECTIVE: The present study aims to compare the efficacy and side effects of a platinum-containing combination regimen and platinum single-drug concurrent chemoradiotherapy (CCRT) in patients with advanced cervical cancer (CC) and to understand the prognostic factors in patients with CC. METHODS: A total of 108 cases of CC treated in Wenzhou Central Hospital were retrospectively selected. Patients in the monotherapy (single-drug) group received external pelvic radiotherapy (RT) and platinum-based single-drug chemotherapy (CT). Patients in the combined group received external pelvic RT and platinum-containing CT. The efficacy, CCRT time, 3-year survival rate after treatment and side effects were compared between the two groups, and the prognostic factors were analysed. RESULTS: The total effective rate was 74.07% in the monotherapy group and 72.22% in the combined group (p = .828). The incidences of myelosuppression, gastrointestinal reaction and abnormal liver function in the grades III-IV combined group were significantly higher than those in the monotherapy group (p < .001; p = .236; p = .022). Furthermore, the CCRT time was significantly longer in the combined group than in the monotherapy group, and the 3-year overall survival (OS) was 81.48% in the monotherapy group and 79.63% in the combined group (p = .643; p = .808). The older the age was, the higher the serum squamous cell carcinoma antigen (SCC-Ag) value before treatment and the shorter the progression-free survival time. In addition, the older the adenocarcinoma (AC) was, the shorter the OS. CONCLUSION: The efficacy of the two regimens in the treatment of advanced CC was similar. However, the side effects increased significantly during combined treatment. PROGNOSTIC FACTORS: A higher patient age, having an AC and stage of IIIa and a high SCC-Ag value before treatment resulted in a relatively low survival rate.

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Protocolos de Quimioterapia Combinada Antineoplásica , Quimioradioterapia , Neoplasias del Cuello Uterino , Humanos , Femenino , Neoplasias del Cuello Uterino/terapia , Neoplasias del Cuello Uterino/mortalidad , Neoplasias del Cuello Uterino/tratamiento farmacológico , Persona de Mediana Edad , Quimioradioterapia/métodos , Quimioradioterapia/efectos adversos , Estudios Retrospectivos , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Anciano , Resultado del Tratamiento , Tasa de Supervivencia , Pronóstico , Cisplatino/administración & dosificación , Cisplatino/uso terapéutico , Cisplatino/efectos adversos , Compuestos Organoplatinos/administración & dosificación , Compuestos Organoplatinos/uso terapéutico , Compuestos Organoplatinos/efectos adversos , Antígenos de Neoplasias , Serpinas

RESUMEN

BACKGROUND: Cervical and breast cancers are among the top 4 leading causes of cancer-related mortality in women. This study aimed to examine age-specific temporal trends in mortality for cervical and breast cancers in urban and rural areas of China from 2009 to 2021. METHODS: Age-specific mortality data for cervical and breast cancers among Chinese women aged 20-84 years were obtained from China's National Disease Surveillance Points system spanning the years 2009 to 2021. Negative binomial regression models were utilized to assess urban-rural differences in mortality rate ratios, while Joinpoint models with estimated average annual percent changes (AAPC) and slopes were employed to compare temporal trends and the acceleration of mortality rates within different age groups. RESULTS: From 2009 to 2021, there was a relative increase in age-specific mortality associated with the two cancers observed in rural areas compared with urban areas. A rising trend in the screening age of 35-64 [AAPC: 4.0%, 95% confidence interval (CI) 0.5-7.6%, P = 0.026] for cervical cancer was noted in rural areas, while a stable trend (AAPC: - 0.7%, 95% CI - 5.8 to 4.6%, P = 0.78) was observed in urban areas. As for breast cancer, a stable trend (AAPC: 0.3%, 95% CI - 0.3 to 0.9%, P = 0.28) was observed in rural areas compared to a decreasing trend (AAPC: - 2.7%, 95% CI - 4.6 to - 0.7%, P = 0.007) in urban areas. Urban-rural differences in mortality rates increased over time for cervical cancer but decreased for breast cancer. Mortality trends for both cervical and breast cancers showed an increase with age across 4 segments, with the most significant surge in mortality observed among the 35-54 age group across urban and rural areas, periods, and regions in China. CONCLUSIONS: Special attention should be given to women aged 35-54 years due to mortality trends and rural-urban disparities. Focusing on vulnerable age groups and addressing rural-urban differences in the delivery of cancer control programs can enhance resource efficiency and promote health equity.

Asunto(s)

Neoplasias de la Mama , Población Rural , Población Urbana , Neoplasias del Cuello Uterino , Humanos , Femenino , Persona de Mediana Edad , Neoplasias de la Mama/mortalidad , Adulto , China/epidemiología , Anciano , Neoplasias del Cuello Uterino/mortalidad , Población Rural/estadística & datos numéricos , Población Rural/tendencias , Población Urbana/estadística & datos numéricos , Población Urbana/tendencias , Anciano de 80 o más Años , Adulto Joven , Mortalidad/tendencias , Factores de Edad

RESUMEN

BACKGROUND: To identify the cut-off values for the number of metastatic lymph nodes (nMLN) and lymph node ratio (LNR) that can predict outcomes in patients with FIGO 2018 IIICp cervical cancer (CC). METHODS: Patients with CC who underwent radical hysterectomy with pelvic lymphadenectomy were identified for a propensity score-matched (PSM) cohort study. A receiver operating characteristic (ROC) curve analysis was performed to determine the critical nMLN and LNR values. Five-year overall survival (OS) and disease-free survival (DFS) rates were compared using Kaplan-Meier and Cox proportional hazard regression analyses. RESULTS: This study included 3,135 CC patients with stage FIGO 2018 IIICp from 47 Chinese hospitals between 2004 and 2018. Based on ROC curve analysis, the cut-off values for nMLN and LNR were 3.5 and 0.11, respectively. The final cohort consisted of nMLN ≤ 3 (n = 2,378) and nMLN > 3 (n = 757) groups and LNR ≤ 0.11 (n = 1,748) and LNR > 0.11 (n = 1,387) groups. Significant differences were found in survival between the nMLN ≤ 3 vs the nMLN > 3 (post-PSM, OS: 76.8% vs 67.9%, P = 0.003; hazard ratio [HR]: 1.411, 95% confidence interval [CI]: 1.108-1.798, P = 0.005; DFS: 65.5% vs 55.3%, P < 0.001; HR: 1.428, 95% CI: 1.175-1.735, P < 0.001), and the LNR ≤ 0.11 and LNR > 0.11 (post-PSM, OS: 82.5% vs 76.9%, P = 0.010; HR: 1.407, 95% CI: 1.103-1.794, P = 0.006; DFS: 72.8% vs 65.1%, P = 0.002; HR: 1.347, 95% CI: 1.110-1.633, P = 0.002) groups. CONCLUSIONS: This study found that nMLN > 3 and LNR > 0.11 were associated with poor prognosis in CC patients.

Asunto(s)

Escisión del Ganglio Linfático , Ganglios Linfáticos , Metástasis Linfática , Estadificación de Neoplasias , Neoplasias del Cuello Uterino , Humanos , Femenino , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/mortalidad , Neoplasias del Cuello Uterino/cirugía , Persona de Mediana Edad , Estudios Retrospectivos , Metástasis Linfática/patología , Pronóstico , Ganglios Linfáticos/patología , Ganglios Linfáticos/cirugía , Adulto , Índice Ganglionar , Histerectomía , Anciano , Puntaje de Propensión , Valor Predictivo de las Pruebas , Estimación de Kaplan-Meier , Supervivencia sin Enfermedad , Curva ROC

RESUMEN

BACKGROUND: This meta-analysis seeks to assess the efficacy and safety of pembrolizumab in individuals with advanced or recurrent cervical cancer. METHODS: Databases from PubMed, Embase, and the Cochrane Library were all thoroughly searched for pertinent research. Outcomes include complete response (CR), partial response (PR), stable disease (SD), disease progression (PD), overall response rate (ORR), disease control rate (DCR), median progression-free survival (mPFS), median overall survival (mOS), and adverse events (AEs) were retrieved for further analysis. RESULTS: Ten trials with 721 patients were included in this meta-analysis. The pooled results for patients with cervical cancer receiving pembrolizumab were as follows: CR (0.06, 95%CI: 0.02-0.10), PR (0.15, 95%CI: 0.08-0.22), SD (0.16, 95%CI: 0.13-0.20), PD (0.50, 95%CI: 0.25-0.75), ORR (0.26, 95%CI: 0.11-0.41) and DCR (0.42, 95%CI: 0.13-0.71), respectively. Regarding survival analysis, the pooled mPFS and mOS were 3.81 and 10.15 months. Subgroup analysis showed that pembrolizumab in combination was more beneficial in CR (0.16 vs. 0.03, p = 0.012), PR (0.24 vs. 0.08, p = 0.032), SD (0.11 vs. 0.19, p = 0.043), ORR (0.42 vs. 0.11, p = 0.014), and mPFS (5.54 months vs. 2.27 months, p < 0.001) than as single agent. The three most common AEs were diarrhoea (0.25), anaemia (0.25), and nausea (0.21), and the incidence of grade 3-5 AEs was significantly lower, rarely surpassing 0.10. CONCLUSIONS: For patients with advanced or recurrent cervical cancer, this systematic review and meta-analysis demonstrated that pembrolizumab had a favourable efficacy and tolerability. Future research will primarily focus on optimising customised regiments that optimally integrate pembrolizumab into new therapies and combination strategies. Designed to maximise patient benefit and efficiently control adverse effects while maintaining a high standard of living.

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This study demonstrated the efficacy and safety of pembrolizumab in individuals with advanced or recurrent cervical cancer. The study found that an upfront combination of chemotherapy and pembrolizumab immunotherapy appears to be a compelling strategy for these patients. More large-scale and multicentre randomised controlled trials will be required in the future to validate the precise benefits of pembrolizumab in new therapies and combination strategies for the treatment of cervical cancer.

Asunto(s)

Anticuerpos Monoclonales Humanizados , Antineoplásicos Inmunológicos , Recurrencia Local de Neoplasia , Neoplasias del Cuello Uterino , Humanos , Neoplasias del Cuello Uterino/tratamiento farmacológico , Neoplasias del Cuello Uterino/mortalidad , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/efectos adversos , Femenino , Recurrencia Local de Neoplasia/tratamiento farmacológico , Antineoplásicos Inmunológicos/efectos adversos , Antineoplásicos Inmunológicos/uso terapéutico , Resultado del Tratamiento , Supervivencia sin Progresión , Persona de Mediana Edad

RESUMEN

BACKGROUND: Cervical cancer incidence is rising in Puerto Rico (PR). Whether the increase is real or reflective of increased diagnostic scrutiny remains unclear. METHODS: Using data from the PR Central Cancer Registry for 2001-2019, we estimated trends of hysterectomy-corrected cervical cancer incidence and mortality rates, overall, and by stage at diagnosis and age. RESULTS: Overall, cervical cancer incidence (per 100,000) increased 1.6%/year (95% CI, -0.5% to 3.8%) from 12.5 to 15.3, with a prominent increase in distant-stage disease (4.5%/year [95% CI, 1.6% to 8.0%]), particularly among screening age eligible (25-64-year-old) women (5.8%/year [95% CI, 2.1% to 10.6%]). Mortality rates in this age-group remained stable during the study period. CONCLUSIONS: Increased occurrence of distant-stage disease among screening-eligible women is troubling and may reflect a real increase. Future research is needed to elucidate the factors underlying these trends. Improved prevention is also an urgent priority to reverse the rising cervical cancer incidence in PR.

Asunto(s)

Neoplasias del Cuello Uterino , Humanos , Femenino , Puerto Rico/epidemiología , Neoplasias del Cuello Uterino/epidemiología , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/mortalidad , Incidencia , Persona de Mediana Edad , Adulto , Anciano , Adulto Joven , Estadificación de Neoplasias , Adolescente , Sistema de Registros

RESUMEN

BACKGROUND: Cancer-associated fibroblasts (CAFs) are crucial components of the cervical cancer tumor microenvironment, playing a significant role in cervical cancer progression, treatment resistance, and immune evasion, but whether the expression of CAF-related genes can predict clinical outcomes in cervical cancer is still unknown. In this study, we sought to analyze genes associated with CAFs through weighted gene co-expression network analysis (WGCNA) and to create a predictive model for CAFs in cervical cancer. METHODS: We acquired transcriptome sequencing data and clinical information on cervical cancer patients from the cancer genome atlas (TCGA) and gene expression omnibus (GEO) databases. WGCNA was conducted to identify genes related to CAFs. We developed a prognostic model based on CAF genes in cervical cancer using the least absolute shrinkage and selection operator (LASSO) Cox regression analysis. Single-cell sequencing data analysis and in vivo experiments for validation of hub genes in CAFs. RESULTS: A prognostic model for cervical cancer was developed based on CAF genes including COL4A1 , LAMC1 , RAMP3 , POSTN , and SERPINF1 . Cervical cancer patients were divided into low- and high-risk groups based on the optimal cutoff value. Patients in the high-risk group had a significantly worse prognosis. Single-cell RNA sequencing data revealed that hub genes in the CAFs risk model were expressed mainly in fibroblasts. The real-time fluorescence quantitative polymerase chain reaction (PCR) results revealed a significant difference in the expression levels of COL4A1 , LAMC1 , POSTN , and SERPINF1 between the cancer group and the normal group ( p < 0.05). Consistently, the results of the immunohistochemical tests exhibited notable variations in COL4A1, LAMC1, RAMP3, POSTN, and SERPINF1 expression between the cancer and normal groups ( p < 0.001). CONCLUSION: The CAF risk model for cervical cancer constructed in this study can be used to predict prognosis, while the CAF hub genes can be utilized as crucial markers for cervical cancer prognosis.

Asunto(s)

Biomarcadores de Tumor , Fibroblastos Asociados al Cáncer , Neoplasias del Cuello Uterino , Humanos , Neoplasias del Cuello Uterino/genética , Neoplasias del Cuello Uterino/mortalidad , Neoplasias del Cuello Uterino/patología , Femenino , Pronóstico , Biomarcadores de Tumor/genética , Microambiente Tumoral

RESUMEN

OBJECTIVE: This meta-analysis aimed to investigate the association between circulating human papillomavirus (HPV) cell-free DNA and oncological outcomes of cervical cancer patients. METHODS: Searches were performed in MEDLINE, Embase, and CENTRAL from their inception until 26 November 2023. Inclusion criteria were: (1) pathologically confirmed cervical cancer with available HPV test results; (2) detection of HPV cell-free DNA was performed in serum/plasma before or at end of treatment; (3) studies reported oncological outcomes of cervical cancer patients according to the levels of HPV cell-free DNA. Data extraction and study quality assessment were performed independently by two authors. Pooled hazard ratios and 95% confidence intervals were calculated using the inverse-variance method for survival outcomes. RESULTS: Five studies were finally included in this meta-analysis. Blood samples were collected from 167 patients before treatment, with 150 individuals available for analysis at the end of treatment. Furthermore, 82 patients with available samples at 3 months post-treatment were included in the analysis. The pooled results indicated a significant association between positive HPV cell-free DNA at end of treatment and worse progression-free survival in patients with cervical cancer (pooled hazard ratio: 5.49; 95 % confidence interval: 2.85-10.58; I2: 0 %). Similar findings were observed in patients with detectable HPV cell-free DNA at 3 months post-treatment (pooled hazard ratio: 7.86; 95 % confidence interval: 3.32-18.60; I2: 0 %). However, the detection of HPV cell-free DNA before treatment was not significantly associated with progression-free survival (pooled hazard ratio: 0.97; 95 % confidence interval: 0.55-1.71; I2: 0 %). CONCLUSION: Cervical cancer patients testing positive for HPV cell-free DNA at the end of treatment or 3 months post-treatment displayed significantly poorer oncological outcomes compared to those testing negative. Thus, personalized monitoring of HPV cell-free DNA holds promise as a prognostic biomarker for patients with cervical cancer.

Asunto(s)

Ácidos Nucleicos Libres de Células , ADN Viral , Infecciones por Papillomavirus , Neoplasias del Cuello Uterino , Humanos , Neoplasias del Cuello Uterino/virología , Neoplasias del Cuello Uterino/sangre , Neoplasias del Cuello Uterino/mortalidad , Femenino , Ácidos Nucleicos Libres de Células/sangre , Pronóstico , ADN Viral/sangre , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/virología , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/sangre , Papillomaviridae/genética , Papillomaviridae/aislamiento & purificación , Virus del Papiloma Humano

RESUMEN

BACKGROUND: Neighborhood socioeconomic deprivation has been linked to adverse health outcomes, yet it is unclear whether neighborhood-level social determinants of health (SDOH) measures affect overall survival in adolescent and young adult patients with cancer. METHODS: This study used a diverse cohort of adolescent and young adult patients with cancer (N = 10 261) seen at MD Anderson Cancer Center. Zip codes were linked to Area Deprivation Index (ADI) values, a validated neighborhood-level SDOH measure, with higher ADI values representing worse SDOH. RESULTS: ADI was statistically significantly worse (P < .050) for Black (61.7) and Hispanic (65.3) patients than for White patients (51.2). Analysis of ADI by cancer type showed statistically significant differences, mainly driven by worse ADI in patients with cervical cancer (62.3) than with other cancers. In multivariable models including sex, age at diagnosis, cancer diagnosis, and race and ethnicity, risk of shorter survival for people residing in neighborhoods with the least favorable ADI quartile was greater than for individuals in the most favorable ADI quartile (hazard ratio = 1.09, 95% confidence interval = 1.00 to 1.19, P = .043). CONCLUSION: Adolescent and young adult patients with cancer and the worst ADI values experienced a nearly 10% increase in risk of dying than patients with more favorable ADI values. This effect was strongest among White adolescent and young adult survivors. Although the magnitude of the effect of ADI on survival was moderate, the presence of a relationship between neighborhood-level SDOH and survival among patients who received care at a tertiary cancer center suggests that ADI is a meaningful predictor of survival. These findings provide intriguing evidence for potential interventions aimed at supporting adolescent and young adult patients with cancer from disadvantaged neighborhoods.

Asunto(s)

Hispánicos o Latinos , Neoplasias , Determinantes Sociales de la Salud , Humanos , Adolescente , Femenino , Masculino , Adulto Joven , Neoplasias/mortalidad , Hispánicos o Latinos/estadística & datos numéricos , Población Blanca/estadística & datos numéricos , Características del Vecindario , Negro o Afroamericano/estadística & datos numéricos , Adulto , Neoplasias del Cuello Uterino/mortalidad , Neoplasias del Cuello Uterino/etnología , Modelos de Riesgos Proporcionales , Características de la Residencia , Factores Socioeconómicos