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Objectives: Quantitatively assess the severity and predict the mortality of interstitial lung disease (ILD) associated with Rheumatoid arthritis (RA) was a challenge for clinicians. This study aimed to construct a radiomics nomogram based on chest computed tomography (CT) imaging by using the ILD-GAP (gender, age, and pulmonary physiology) index system for clinical management. Methods: Chest CT images of patients with RA-ILD were retrospectively analyzed and staged using the ILD-GAP index system. The balanced dataset was then divided into training and testing cohorts at a 7:3 ratio. A clinical factor model was created using demographic and serum analysis data, and a radiomics signature was developed from radiomics features extracted from the CT images. Combined with the radiomics signature and independent clinical factors, a nomogram model was established based on the Rad-score and clinical factors. The model capabilities were measured by operating characteristic curves, calibration curves and decision curves analyses. Results: A total of 177 patients were divided into two groups (Group I, n = 107; Group II, n = 63). Krebs von den Lungen-6, and nineteen radiomics features were used to build the nomogram, which showed favorable calibration and discrimination in the training cohort [AUC, 0.948 (95% CI: 0.910-0.986)] and the testing validation cohort [AUC, 0.923 (95% CI: 0.853-0.993)]. Decision curve analysis demonstrated that the nomogram performed well in terms of clinical usefulness. Conclusion: The CT-based radiomics nomogram model achieved favorable efficacy in predicting low-risk RA-ILD patients.

Asunto(s)

Artritis Reumatoide , Enfermedades Pulmonares Intersticiales , Mucina-1 , Nomogramas , Radiómica , Tomografía Computarizada por Rayos X , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Artritis Reumatoide/sangre , Artritis Reumatoide/complicaciones , Biomarcadores/sangre , Enfermedades Pulmonares Intersticiales/sangre , Enfermedades Pulmonares Intersticiales/diagnóstico por imagen , Enfermedades Pulmonares Intersticiales/etiología , Mucina-1/sangre , Estudios Retrospectivos , Factores de Riesgo , Índice de Severidad de la Enfermedad , Tomografía Computarizada por Rayos X/métodos

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The development of integrated analytical devices is crucial for advancing next-generation point-of-care platforms. Herein, we describe a facile synthesis of a strongly catalytic and durable Nitrogen-doped graphene oxide decorated platinum cobalt (NGO-PtCo) nanocomposite that is conjugated with target-specific DNA aptamer (i-e. MUC1) and grown on carbon fiber. Benefitting from the combined features of the high electrochemical surface area of N-doped GO, high capacitance and stabilization by Co, and high kinetic performance by Pt, a robust, multifunctional, and flexible nanotransducer surface was created. The designed platform was applied for the specific detection of a blood-based oncomarker, CA15-3. The electrochemical characterization proved that nanosurface provides a highly conductive and proficient immobilization support with a strong bio-affinity towards MUC1 aptamer. The specific interaction between CA15-3 and the aptamer alters the surface properties of the aptasensor and the electroactive signal probe generated a remarkable increase in signal intensity. The sensor exhibited a wide dynamic range of 5.0 × 10-2 -200 U mL-1, a low limit of detection (LOD) of 4.1 × 10-2 U mL-1, and good reproducibility. The analysis of spiked serum samples revealed outstanding recoveries of up to 100.03 %, by the proposed aptasensor. The aptasensor design opens new revelations in the reliable detection of tumor biomarkers for timely cancer diagnosis.

Asunto(s)

Aptámeros de Nucleótidos , Técnicas Biosensibles , Fibra de Carbono , Cobalto , Técnicas Electroquímicas , Grafito , Mucina-1 , Nanocompuestos , Platino (Metal) , Aptámeros de Nucleótidos/química , Técnicas Electroquímicas/métodos , Grafito/química , Humanos , Mucina-1/sangre , Mucina-1/análisis , Cobalto/química , Nanocompuestos/química , Platino (Metal)/química , Técnicas Biosensibles/métodos , Fibra de Carbono/química , Límite de Detección

RESUMEN

INTRODUCTION: The natural course of interstitial lung disease (ILD) in patients with systemic autoimmune rheumatic diseases (SARD) varies significantly and is linked to considerable morbidity and mortality. Therefore, effective screening is crucial for early detection of SARD-ILD. Biomarkers associated with mucin 1, Krebs von den Lungen-6 (KL-6) and carbohydrate antigen 15-3 (CA 15-3), are increased in various ILD. This study aimed to assess the diagnostic accuracy of the serum biomarker CA 15-3 as a potential screening tool for ILD in patients newly diagnosed with SARD. METHODS: Conducted as a single-center cross-sectional study, the research included newly diagnosed SARD patients consecutively examined for ILD according to the algorithm. All included patients underwent chest high-resolution CT scans (HRCT), and serum levels of CA 15-3, KL-6, and lactate dehydrogenase (LDH) were measured and correlated with other variables associated with possible ILD presence. RESULTS: Serum biomarker levels, specifically CA 15-3 and LDH, are significantly higher in ILD-positive patients (P<0.001 for both). An inverse relationship is observed between higher FVC values and lower CA 15-3 levels (Rho=-0.291, P=0.007). Similarly, higher DLCO values are associated with lower CA 15-3 levels (Rho=-0.317, P=0.003). Our findings revealed that elevated CA 15-3 levels are positively correlated with higher levels of KL-6 (Rho=0.268, P=0.01) and LDH (Rho=0.227, P=0.04). With a cut-off value of 24 U/mL, CA 15-3 showed the highest sensitivity and specificity (AUC=0.807, specificity=95.7%, sensitivity=71.1%). CA 15-3 emerged as the most significant predictor of a positive HRCT finding, accurately classifying 83% of cases. CONCLUSION: These results suggest that CA 15-3 shows promise as a valuable serum biomarker for screening SARD patients for ILD in routine clinical practice.

Asunto(s)

Enfermedades Autoinmunes , Biomarcadores , Enfermedades Pulmonares Intersticiales , Mucina-1 , Enfermedades Reumáticas , Humanos , Enfermedades Pulmonares Intersticiales/sangre , Enfermedades Pulmonares Intersticiales/diagnóstico , Enfermedades Pulmonares Intersticiales/etiología , Enfermedades Pulmonares Intersticiales/diagnóstico por imagen , Estudios Transversales , Femenino , Masculino , Persona de Mediana Edad , Enfermedades Reumáticas/sangre , Enfermedades Reumáticas/complicaciones , Biomarcadores/sangre , Enfermedades Autoinmunes/sangre , Enfermedades Autoinmunes/diagnóstico , Adulto , Mucina-1/sangre , Anciano , Tomografía Computarizada por Rayos X , L-Lactato Deshidrogenasa/sangre

RESUMEN

Serum KL-6 is elevated in patients with various diseases such as interstitial lung disease(ILD), lung cancer, or breast cancer. However, whether serum KL-6 levels would be increased in patients with gastric cancer remains unclear. In this study, we aimed to reveal the frequency and characteristics of patients with gastric cancer exhibiting high serum KL-6 levels and no ILD. Therefore, we retrospectively reviewed the medical records of patients with gastric cancer and serum KL-6 levels measured prior to nivolumab-containing therapies. No patients had ILD at pretreatment. The median serum KL-6 level at pretreatment was 314 U/mL. Serum KL-6 levels increased above 500 U/mL in 16 of 56 patients at pretreatment. Serum KL-6 levels were higher in smokers and ex-smokers than in never-smokers as well as in patients with multiple metastases than in those with a single metastatic lesion. Moreover, we conducted a representative case presentation. Due to the increasing immune checkpoint inhibitor use in gastric cancer management, awareness concerning potentially increased serum KL-6 levels in patients with gastric cancer without ILD would be useful for physicians due to the more frequent opportunities to measure serum KL-6 levels for early detection and differential diagnosis of ILD.

Asunto(s)

Enfermedades Pulmonares Intersticiales , Mucina-1 , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/sangre , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/patología , Femenino , Masculino , Mucina-1/sangre , Anciano , Persona de Mediana Edad , Enfermedades Pulmonares Intersticiales/sangre , Estudios Retrospectivos , Metástasis de la Neoplasia , Anciano de 80 o más Años

RESUMEN

BACKGROUND: Novel progressive fibrotic phenotype has recently been proposed characterized by progressive and inexorable worsening of the disease. Krebs von den Lungen-6 (KL-6) has been proposed as fibrotic-ILD biomarker. We aimed to assess the role of KL-6 in fibrotic-ILD and the progressive phenotype in accordance with serial serum KL-6. METHODS: 107 patients were enrolled in the study (median age,IQR, 65(54-71)y/o) followed at respiratory diseases and rheumatology units of University of Siena. Thirty-five had diagnoses of IPF, 18 sarcoidosis, 10 PLCH, 5 LAM, 24 fibrotic HP(fHP), 13 RA (4/13 RA-ILD) and 22 SSc (18/22 SSc-ILD). Serial serum samples were collected before therapy (t0) and 24 months later (t1) from IPF, SSc- and RA-ILD patients. Twenty-two healthy controls (HC) were enrolled. Serum samples were assayed for KL-6 concentrations (Fujirebio Europe, Gent, Belgium). RESULTS: Higher KL-6 concentrations were reported in IPF, fHP and SSc-ILD patients than HC (p<0.0001). KL-6 cut-off value of 885 U/mL identified fibrotic-ILD patients. Logistic regression analysis indicated KL-6 (p=0.004) and smoking-habit (p=0.005) affected the ILD diagnosis. The decision tree model showed KL-6>1145 U/mL, DLco≤60.15 %, FVC≤86 % to classify 86 % IPF patients. Inverse correlation between T0-KL-6 and T1-FVC%(r=-0.314, p=0.046) and T1-DLco%(r=-0.327, p=0.038) in the progressive group. CONCLUSION: KL-6 proved to be a reliable marker for diagnosis and prognosis of fibrotic ILD patients with predictive value in progressive fibrotic patients and a useful marker to identify the new and similar progressive phenotype of IPF and SSc-ILD patients assessing the functional progression in accordance with serial serum KL-6 measurements.

Asunto(s)

Biomarcadores , Enfermedades Pulmonares Intersticiales , Mucina-1 , Fenotipo , Humanos , Biomarcadores/sangre , Mucina-1/sangre , Persona de Mediana Edad , Masculino , Femenino , Enfermedades Pulmonares Intersticiales/sangre , Enfermedades Pulmonares Intersticiales/patología , Anciano , Progresión de la Enfermedad , Fibrosis/sangre

RESUMEN

Objective: The aim of this study was to explore the potential values of Krebs von den Lungen-6 (KL-6), neutrophil to lymphocyte ratio (NLR), systemic immune inflammation (SII), platelet to lymphocyte ratio (PLR), monocyte to lymphocyte ratio (MLR) and red blood cell distribution width (RDW) in the diagnosis and evaluation of the severity of connective tissue disease-associated interstitial lung disease (CTD-ILD). Methods: A total of 140 connective tissue disease (CTD) patients and 85 CTD-ILD patients were recruited for this study at Shanxi Provincial People's Hospital from May 2022 to May 2023. Patients were divided into subgroups based on medication history and CTD subtypes to compare and analyze the clinical data and laboratory parameters of CTD-ILD patients and CTD patients. The receiver operating characteristic curve (ROC) was used to evaluate the diagnostic efficacy of KL-6, NLR, SII, PLR, MLR, and RDW in identifying CTD-ILD patients from CTD patients. A Spearman correlation analysis was conducted to elucidate the correlations between these markers and the lung function parameters of forced vital capacity (FVC, %), forced expired volume in one second (FEV1, %), and diffusing capacity of carbon monoxide (DLCO, %). Finally, binary logistic regression analysis was applied to discern the independent risk factors for CTD-ILD. Results: NLR, SII, MLR, RDW, and KL-6 displayed significant statistical differences in the experimental groups. In both untreated and treated subgroups, KL-6 displayed higher values for CTD-ILD than CTD among all CTD subtypes. In untreated subgroups, there were significant differences in MLR levels between rheumatoid arthritis (RA) and RA-ILD patients and in NLR levels between Sjögren syndrome (SjS) and SjS-ILD patients. There were also significant differences in RDW-SD between the "other CTD" and "other CTD-ILD" groups. In treated subgroups, there were significant differences in both RDW-SD and RDW-CV between RA and RA-ILD patients and in NLR, SII, MLR, PLR, and RDW-SD between "other CTD" and "other CTD-ILD" groups. ROC revealed that KL-6 emerged as the most effective predictor for CTD-ILD in both treated and untreated groups. The multivariate logistic regression analysis results showed that both KL-6 and age were independent risk factors for CTD-ILD. NLR, SII, and PLR were negatively correlated with DLCO (%) in the untreated CTD-ILD group, and KL-6 was negatively correlated with various lung function parameters in both treated and untreated CTD-ILD groups. Conclusion: KL-6 emerged as the most promising biomarker for diagnosing CTD-ILD and assessing its severity. The diagnostic value of KL-6 was unaffected by medication interference and surpassed the value of other parameters, such as NLR, SII, MLR, and RDW. The diagnostic value of RDW-SD was higher than that of RDW-CV in CTD-ILD patients. NLR, SII, MLR, and PLR have potential value in diagnosing the different types of CTD-ILD.

Asunto(s)

Biomarcadores , Enfermedades del Tejido Conjuntivo , Enfermedades Pulmonares Intersticiales , Mucina-1 , Humanos , Enfermedades Pulmonares Intersticiales/sangre , Enfermedades Pulmonares Intersticiales/diagnóstico , Femenino , Masculino , Persona de Mediana Edad , Mucina-1/sangre , Enfermedades del Tejido Conjuntivo/complicaciones , Enfermedades del Tejido Conjuntivo/sangre , Enfermedades del Tejido Conjuntivo/diagnóstico , Biomarcadores/sangre , Índice de Severidad de la Enfermedad , Anciano , Neutrófilos , Adulto , Índices de Eritrocitos , Curva ROC , Valor Predictivo de las Pruebas , Pruebas de Función Respiratoria , Linfocitos

RESUMEN

BACKGROUND: The serum markers Krebs von den Lungen-6 (KL-6), surfactant protein A (SP-A), and surfactant protein D (SP-D) have been used for the diagnosis, differential diagnosis, and prognosis prediction of interstitial pneumonia. However, the significance of measuring the serum and bronchoalveolar lavage fluid (BALF) KL-6, SP-D, and SP-A levels in predicting the prognosis of chronic fibrosing interstitial pneumonia (CFIP), idiopathic pulmonary fibrosis, and idiopathic nonspecific interstitial pneumonia remains unclear. We aimed to clarify the significance of measuring the serum and BALF KL-6, SP-A, and SP-D levels in predicting the prognosis of patients with CFIP. METHODS: Among 173 patients who were diagnosed with CFIP between September 2008 and February 2021, 39 who underwent bronchoalveolar lavage were included in this study. Among these, patients experiencing an annual decrease in forced vital capacity (FVC) of ≥10% or those facing challenges in undergoing follow-up pulmonary function tests owing to significant deterioration in pulmonary function were categorized as the rapidly progress group. Conversely, individuals with an annual decrease in the FVC of <10% were classified into the slowly progress group. The serum and BALF KL-6, SP-D, and SP-A levels, as well as BALF/serum SP-D and SP-A ratios were compared between the two groups. RESULTS: Among the patients with CFIP, the BALF SP-D level (p=0.0111), BALF SP-A level (p<0.0010), BALF/serum SP-D ratio (p=0.0051), and BALF/serum SP-A ratio (p<0.0010) were significantly lower in the rapidly than in the slowly progress group (p<0.0010). The receiver operating characteristics analysis results demonstrated excellent performance for diagnosing patients with CFIP, with the BALF SP-D level (area under the curve [AUC], 0.7424), BALF SP-A level (AUC, 0.8842), BALF/serum SP-D ratio (AUC, 0.7673), and BALF/serum SP-A ratio (AUC, 0.8556). Moreover, the BALF SP-A level showed a notably superior CFIP diagnostic capability. Survival analysis using the Kaplan-Meier method revealed that patients with a BALF SP-A level of <1500 ng/mL and BALF/serum SP-A ratio of <15.0 had poor prognoses. CONCLUSIONS: Our results suggest that BALF SP-A measurement may be useful for predicting the prognosis in patients with CFIP.

Asunto(s)

Biomarcadores , Líquido del Lavado Bronquioalveolar , Mucina-1 , Proteína A Asociada a Surfactante Pulmonar , Proteína D Asociada a Surfactante Pulmonar , Humanos , Proteína D Asociada a Surfactante Pulmonar/sangre , Proteína D Asociada a Surfactante Pulmonar/metabolismo , Líquido del Lavado Bronquioalveolar/química , Mucina-1/sangre , Mucina-1/análisis , Femenino , Masculino , Estudios Retrospectivos , Proteína A Asociada a Surfactante Pulmonar/sangre , Proteína A Asociada a Surfactante Pulmonar/metabolismo , Proteína A Asociada a Surfactante Pulmonar/análisis , Anciano , Persona de Mediana Edad , Pronóstico , Biomarcadores/sangre , Biomarcadores/análisis , Fibrosis Pulmonar Idiopática/sangre , Fibrosis Pulmonar Idiopática/diagnóstico , Fibrosis Pulmonar Idiopática/metabolismo , Enfermedades Pulmonares Intersticiales/sangre , Enfermedades Pulmonares Intersticiales/diagnóstico , Enfermedades Pulmonares Intersticiales/metabolismo , Curva ROC , Capacidad Vital , Enfermedad Crónica

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This study developed an innovative biosensor strategy for the sensitive and selective detection of canine mammary tumor biomarkers, cancer antigen 15-3 (CA 15-3) and mucin 1 (MUC-1), integrating green silver nanoparticles (GAgNPs) with machine learning (ML) algorithms to achieve high diagnostic accuracy and potential for noninvasive early detection. The GAgNPs-enhanced electrochemical biosensor demonstrated selective detection of CA 15-3 in serum and MUC-1 in tissue homogenates, with limits of detection (LODs) of 0.07 and 0.11 U mL-1, respectively. The nanoscale dimensions of the GAgNPs endowed them with electrochemically active surface areas, facilitating sensitive biomarker detection. Experimental studies targeted CA 15-3 and MUC-1 biomarkers in clinical samples, and the biosensor exhibited ease of use and good selectivity. Furthermore, ML algorithms were employed to analyze the electrochemical data and predict biomarker concentrations, enhancing the diagnostic accuracy. The Random Forest algorithm achieved 98% accuracy in tumor presence prediction, while an Artificial Neural Network attained 76% accuracy in CA 15-3-based tumor grade classification. The integration of ML techniques with the GAgNPs-based biosensor offers a promising approach for noninvasive, accurate, and early detection of canine mammary tumors, potentially revolutionizing veterinary diagnostics. This multilayered strategy, combining eco-friendly nanomaterials, electrochemical sensing, and ML algorithms, holds significant potential for advancing both biomedical research and clinical practice in the field of canine mammary tumor diagnostics.

Asunto(s)

Biomarcadores de Tumor , Técnicas Biosensibles , Técnicas Electroquímicas , Aprendizaje Automático , Neoplasias Mamarias Animales , Nanopartículas del Metal , Plata , Animales , Perros , Plata/química , Nanopartículas del Metal/química , Biomarcadores de Tumor/sangre , Biomarcadores de Tumor/análisis , Neoplasias Mamarias Animales/diagnóstico , Neoplasias Mamarias Animales/sangre , Técnicas Electroquímicas/métodos , Femenino , Técnicas Biosensibles/métodos , Mucina-1/sangre , Mucina-1/análisis , Enfermedades de los Perros/diagnóstico , Enfermedades de los Perros/sangre , Límite de Detección

RESUMEN

BACKGROUND: Anti-synthetase syndrome-associated interstitial lung disease (ASS-ILD) may occur without myositis. Although a recent Japanese guide proposed a watch-and-wait approach for chronic ASS-ILD without obvious progression, the natural history of this subgroup and the appropriateness of the watch-and-wait approach remain unclear. We aimed to describe the natural history of ASS-ILD, that is sufficiently indolent to be a candidate for the watch-and-wait approach. METHODS: Among consecutive patients with ASS-ILD, we retrospectively identified those without myositis, acute/subacute onset, and significant lung function impairment, which qualified them as indolent-ASS-ILD cases, and described their natural course. Additionally, we evaluated the risk factors for fibrosis progression on computed tomography (CT) using the Cox proportional hazards model. RESULTS: Among 80 patients with ASS-ILD, we identified 33 with indolent-ASS-ILD, all of whom were initially followed up with a watch-and-wait approach. Among 30 patients with sufficient follow-up data, 27 (90%) showed a stable course without treatment over 24 months. Subsequently, four patients experienced ≥10% relative forced vital capacity (FVC) decline without treatment during a median follow-up duration of 81 months. Seven patients showed fibrosis progression with >10% increase in the total lung area on CT. Higher levels of Krebs von den Lungen-6 (KL-6) and surfactant protein-D (SP-D) were associated with fibrosis progression on CT. CONCLUSION: Most patients with indolent-ASS-ILD did not experience ≥10% relative FVC decline over five years without treatment. However, fibrosis progression on CT, which seemed to precede significant FVC decline, occurred more frequently, especially in patients with higher KL-6 and SP-D levels.

Asunto(s)

Progresión de la Enfermedad , Enfermedades Pulmonares Intersticiales , Tomografía Computarizada por Rayos X , Humanos , Enfermedades Pulmonares Intersticiales/etiología , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Anciano , Capacidad Vital , Mucina-1/sangre , Factores de Riesgo , Miositis/complicaciones

RESUMEN

AIM: To evaluate whether seasonal changes influence fluctuations in serum Krebs von den Lungen-6 (KL-6) levels in systemic sclerosis-related interstitial lung disease (SSc-ILD). METHODS: Summer was defined as the period between July and September, and winter as between December and February. The study was conducted between 2015 and 2016, with a focus on these two seasons. A diagnosis of ILD and ILD progression overtime were evaluated using chest computed tomography. Among patients with SSc-ILD, those with data on serum KL-6 and lactate dehydrogenase (LDH) levels in the 2015 winter, 2015 summer, and 2016 winter seasons were included. Patients with comorbidities that could affect serum KL-6 levels were excluded. RESULTS: Of 60 patients with SSc-ILD, 52 (86.7%) had stable ILD, 5 (8.3%) had worsened ILD, and 3 (5.0%) had improved ILD. Serum KL-6 levels were significantly higher during the winter than those during the summer (2015 winter vs. 2015 summer: 649 U/mL vs. 585 U/mL, p < .0001; 2016 winter vs. 2015 summer: 690 U/mL vs. 585 U/mL, p < .0001). No significant differences were observed between the winters of 2015 and 2016 (649 U/mL vs. 690 U/mL, p = .78). However, serum LDH levels did not exhibit seasonal fluctuations (2015 winter vs. 2015 summer: 203 U/L vs. 199 U/L, p = .3; 2016 winter vs. 2015 summer: 201 U/L vs. 199 U/L, p = .6; 2015 winter vs. 2016 winter: 203 U/L vs. 201 U/L, p = .24). CONCLUSION: Seasonal fluctuations in serum KL-6 levels were observed in patients with SSc-ILD.

Asunto(s)

Biomarcadores , Enfermedades Pulmonares Intersticiales , Mucina-1 , Esclerodermia Sistémica , Estaciones del Año , Humanos , Enfermedades Pulmonares Intersticiales/sangre , Enfermedades Pulmonares Intersticiales/diagnóstico , Enfermedades Pulmonares Intersticiales/etiología , Mucina-1/sangre , Femenino , Masculino , Persona de Mediana Edad , Biomarcadores/sangre , Esclerodermia Sistémica/sangre , Esclerodermia Sistémica/complicaciones , Esclerodermia Sistémica/diagnóstico , Anciano , Factores de Tiempo , Progresión de la Enfermedad , Adulto , Estudios Retrospectivos , Tomografía Computarizada por Rayos X , Regulación hacia Arriba

RESUMEN

BACKGROUND: The five-year prognosis for patients with late-stage high-grade serous carcinoma (HGSC) remains dismal, underscoring the critical need for identifying early-stage biomarkers. This study explores the potential of extracellular vesicles (EVs) circulating in blood, which are believed to harbor proteomic cargo reflective of the HGSC microenvironment, as a source for biomarker discovery. RESULTS: We conducted a comprehensive proteomic profiling of EVs isolated from blood plasma, ascites, and cell lines of patients, employing both data-dependent (DDA) and data-independent acquisition (DIA) methods to construct a spectral library tailored for targeted proteomics. Our investigation aimed at uncovering novel biomarkers for the early detection of HGSC by comparing the proteomic signatures of EVs from women with HGSC to those with benign gynecological conditions. The initial cohort, comprising 19 donors, utilized DDA proteomics for spectral library development. The subsequent cohort, involving 30 HGSC patients and 30 control subjects, employed DIA proteomics for a similar purpose. Support vector machine (SVM) classification was applied in both cohorts to identify combinatorial biomarkers with high specificity and sensitivity (ROC-AUC > 0.90). Notably, MUC1 emerged as a significant biomarker in both cohorts when used in combination with additional biomarkers. Validation through an ELISA assay on a subset of benign (n = 18), Stage I (n = 9), and stage II (n = 9) plasma samples corroborated the diagnostic utility of MUC1 in the early-stage detection of HGSC. CONCLUSIONS: This study highlights the value of EV-based proteomic analysis in the discovery of combinatorial biomarkers for early ovarian cancer detection.

Asunto(s)

Biomarcadores de Tumor , Detección Precoz del Cáncer , Vesículas Extracelulares , Mucina-1 , Neoplasias Ováricas , Proteómica , Humanos , Femenino , Vesículas Extracelulares/metabolismo , Proteómica/métodos , Neoplasias Ováricas/sangre , Neoplasias Ováricas/diagnóstico , Neoplasias Ováricas/patología , Neoplasias Ováricas/metabolismo , Biomarcadores de Tumor/sangre , Detección Precoz del Cáncer/métodos , Persona de Mediana Edad , Mucina-1/sangre , Cistadenocarcinoma Seroso/sangre , Cistadenocarcinoma Seroso/diagnóstico , Cistadenocarcinoma Seroso/metabolismo , Cistadenocarcinoma Seroso/patología , Anciano , Clasificación del Tumor , Adulto

RESUMEN

Worldwide, female breast cancer (BC) has surpassed lung cancer as the most commonly diagnosed cancer. Early diagnosis of cancer recurrence can provide substantial benefits for BC patients who are at high risk of relapse. We aimed to investigate the role of ALU 247, ALU 115, cfDNA integrity index, CA15-3 and CEA as potential diagnostic markers in BC patients and as markers for early prediction of recurrence. Fifty BC patients (10 patients showed recurrence), 26 BBD patients and 22 healthy controls were included. Real-time q-PCR was used to measure the concentration of ALU 247 and ALU 115 in plasma then cfDNA integrity index was calculated. "ECLIA" was used to measure the concentration of CA15-3 and CEA in serum. Our results showed significant higher levels of ALU 247, ALU 115, CA15-3 and CEA in BC patients in comparison to healthy controls (P=0.02, 0.008, <0.001 and < 0.001 respectively). Also, cfDNA integrity index was higher in BC patients in comparison to healthy controls but statistically insignificance (p = 0.46). In recurrent BC patients; ALU 247, ALU 115, cfDNA integrity index, CA15-3 and CEA levels were higher compared to non-recurrent BC patients but with no statistic significant (p = 0.46, 0.59, 0.09, 0.85 and 0.84 respectively). This may result from the short period of follow up (1-2 years) and the relatively small sample size due to exclusion of patients with chronic diseases or inflammation as well as those who received therapy or post-surgery. By using the ROC curve, the sensitivity of ALU 247, ALU 115, CA15-3 and CEA for discriminating BC patients from BBD patients and healthy controls was 79 %, 79.2 %, 76.0 % and 88.0 % respectively. This study suggested that ALU 247, ALU 115, CA15-3 and CEA could be promising non-invasive markers of BC for diagnosis and early prediction of recurrence after validation in large-scale future studies.

Asunto(s)

Biomarcadores de Tumor , Neoplasias de la Mama , ADN Tumoral Circulante , Recurrencia Local de Neoplasia , Humanos , Femenino , Neoplasias de la Mama/sangre , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/genética , Egipto , Biomarcadores de Tumor/sangre , Persona de Mediana Edad , Recurrencia Local de Neoplasia/sangre , Recurrencia Local de Neoplasia/diagnóstico , Adulto , ADN Tumoral Circulante/sangre , Elementos Alu/genética , Mucina-1/sangre , Antígeno Carcinoembrionario/sangre , Estudios de Casos y Controles

RESUMEN

Pancreatic cancer is one of the deadliest cancers worldwide, mainly due to late diagnosis. Therefore, there is an urgent need for novel diagnostic approaches to identify the disease as early as possible. We have developed a diagnostic assay for pancreatic cancer based on the detection of naturally occurring tumor associated autoantibodies against Mucin-1 (MUC1) using engineered glycopeptides on nanoparticle probes. We used a structure-guided approach to develop unnatural glycopeptides as model antigens for tumor-associated MUC1. We designed a collection of 13 glycopeptides to bind either SM3 or 5E5, two monoclonal antibodies with distinct epitopes known to recognize tumor associated MUC1. Glycopeptide binding to SM3 or 5E5 was confirmed by surface plasmon resonance and rationalized by molecular dynamics simulations. These model antigens were conjugated to gold nanoparticles and used in a dot-blot assay to detect autoantibodies in serum samples from pancreatic cancer patients and healthy volunteers. Nanoparticle probes with glycopeptides displaying the SM3 epitope did not have diagnostic potential. Instead, nanoparticle probes displaying glycopeptides with high affinity for 5E5 could discriminate between cancer patients and healthy controls. Remarkably, the best-discriminating probes show significantly better true and false positive rates than the current clinical biomarkers CA19-9 and carcinoembryonic antigen (CEA).

Asunto(s)

Autoanticuerpos , Glicopéptidos , Mucina-1 , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/inmunología , Neoplasias Pancreáticas/sangre , Mucina-1/inmunología , Mucina-1/sangre , Mucina-1/química , Glicopéptidos/inmunología , Glicopéptidos/química , Autoanticuerpos/sangre , Autoanticuerpos/inmunología , Autoanticuerpos/química , Nanopartículas del Metal/química , Oro/química , Anticuerpos Monoclonales/inmunología , Anticuerpos Monoclonales/química , Nanopartículas/química

RESUMEN

BACKGROUND: Interstitial lung disease (ILD) is a common pulmonary manifestation of rheumatoid arthritis (RA) and is associated with a poor prognosis. However, the role of blood biomarkers in RA-associated interstitial lung disease (RA-ILD) is ill-defined. We aim to evaluate the role of YKL-40 and Krebs von den Lungen-6 (KL-6) in the diagnosis and severity evaluation of RA-ILD. METHODS: 45 RA-non-ILD patients and 38 RA-ILD patients were included. The clinical data and the levels of YKL-40 and KL-6 were measured and collected for all patients. The risk factors for RA-ILD were analyzed and their correlation with relevant indicators and predictive value for RA-ILD was explored. RESULTS: The levels of YKL-40 and KL-6 in RA-ILD patients were higher than RA-non-ILD patients (p < .001). Both YKL-40 and KL-6 were correlated with the incidence of RA-ILD. The predictive power of combined KL-6 and YKL-40 for the presence of ILD was 0.789, with a sensitivity and specificity at 73.7% and 73.3%, respectively. In RA-ILD patients, both YKL-40 and KL-6 were positively correlated with the Scleroderma Lung Study (SLS) I score and negatively correlated with pulmonary function. CONCLUSIONS: KL-6 and YKL-40 might be a useful biomarker in the diagnosis and severity evaluation of RA-ILD.

Asunto(s)

Artritis Reumatoide , Biomarcadores , Proteína 1 Similar a Quitinasa-3 , Enfermedades Pulmonares Intersticiales , Mucina-1 , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Artritis Reumatoide/sangre , Artritis Reumatoide/diagnóstico , Artritis Reumatoide/complicaciones , Biomarcadores/sangre , Proteína 1 Similar a Quitinasa-3/sangre , Enfermedades Pulmonares Intersticiales/sangre , Enfermedades Pulmonares Intersticiales/diagnóstico , Enfermedades Pulmonares Intersticiales/etiología , Mucina-1/sangre , Valor Predictivo de las Pruebas , Pronóstico , Sensibilidad y Especificidad , Índice de Severidad de la Enfermedad

RESUMEN

BACKGROUND: Cancers of ductal origin often express glycoprotein mucin 1 (MUC1), also known as CA15.3, with higher levels leading to poor prognosis. Conversely, anti-MUC1 antibodies develop in some patients, leading to better prognosis. We sought to identify epidemiologic factors associated with CA15.3 antigen or antibody levels. METHODS: Levels of CA15.3 antigen and anti-CA15.3 IgG antibodies were measured in archived sera from 2,302 mostly healthy women from the National Health and Nutritional Survey; and epidemiologic predictors of their levels were examined using multivariate and correlational analyses. RESULTS: Among racial groups, Black women had the highest levels of CA15.3 antigen and lowest levels of antibodies. Increasing body mass index and current smoking were associated with low anti-CA15.3 antibody levels. Low CA15.3 antigen levels were seen in oral contraceptive users and high levels in women who were pregnant or lactating at the time of blood collection, with the latter group also having high antibody levels. Past reproductive events associated with high antigen levels included the following: later age at menarche, having given birth, and history of endometriosis. Lower antigen levels were seen with increasing duration of OC use. Anti-CA15.3 antibody levels decreased with an increasing estimated number of ovulatory years. CONCLUSIONS: Key determinants of CA.15.3 antigen or antibody levels include the following: race, body mass index, smoking, later menarche, childbirth, number of ovulatory cycles, and endometriosis. IMPACT: This study supports the premise that known epidemiologic factors affecting risk for or survival after MUC1-expressing cancers may, at least partially, operate through their association with CA15.3 antigen or antibody levels.

Asunto(s)

Mucina-1 , Encuestas Nutricionales , Humanos , Femenino , Mucina-1/inmunología , Mucina-1/sangre , Persona de Mediana Edad , Adulto , Anciano , Biomarcadores de Tumor/sangre , Adulto Joven

RESUMEN

OBJECTIVES: To study the prevalence of tumor marker (TM) carcinoembryonic antigen (CEA), cancer antigen 125 (CA 125), and cancer antigen 15-3 (CA 15-3) levels in the Saudi population, based on gender, age, and demographic region, and whether the patients were referred by a hospital or self-referred. METHODS: Retrospective analysis was carried out on 7,019 samples gathered from the Western, Northern, Central, Southern, and Eastern regions of Saudi Arabia between 2021-2022. The TMs were categorized into normal and abnormal levels, according to the reference ranges. Statistical analysis was carried out to assess the relations between variants (age groups, gender, and demographic regions) using the Chi-square test, and their correlations were assessed using Spearman's test. RESULTS: Among all patients, CEA, CA 125, and CA 15-3 levels were found to be significantly correlated with age (p=0.0001). The CEA and CA 15-3 levels increased in both males and females with age. The CA 125 was shown to have an abnormally increased level in males with age. CONCLUSION: Increased levels of CEA, CA 125, and CA 15-3 TMs in the study population were significantly correlated with age. The CEA and CA 15-3 levels were within the normal range, while CA 125 levels were above the normal range in the older male population. These results suggest that the utilization of such TMs is age dependent and would have validity if applied with other parameters.

Asunto(s)

Biomarcadores de Tumor , Antígeno Ca-125 , Antígeno Carcinoembrionario , Mucina-1 , Humanos , Arabia Saudita/epidemiología , Antígeno Carcinoembrionario/sangre , Masculino , Femenino , Persona de Mediana Edad , Biomarcadores de Tumor/sangre , Mucina-1/sangre , Antígeno Ca-125/sangre , Adulto , Estudios Retrospectivos , Anciano , Adolescente , Adulto Joven , Prevalencia , Anciano de 80 o más Años , Niño , Factores de Edad

RESUMEN

The development of an ultrasensitive and precise measurement of a breast cancer biomarker (cancer antigen 15-3; CA15-3) in complex human serum is essential for the early diagnosis of cancer in groups of healthy populations and the treatment of patients. However, currently available testing technologies suffer from insufficient sensitivity toward CA15-3, which severely limits early large-scale screening of breast cancer patients. We report a versatile electrochemical immunoassay method based on atomically cobalt-dispersed nitrogen-doped carbon (Co-NC)-modified disposable screen-printed carbon electrode (SPCE) with alkaline phosphatase (ALP) and its metabolite, ascorbic acid 2-phosphate (AAP), as the electrochemical labeling and redox signaling unit for sensitive detection of low-abundance CA15-3. During electrochemical detection by differential pulse voltammetry (DPV), it was found that the Co-NC-SPCE electrode did not have a current signal response to the AAP substrate; however, it had an extremely favorable response current to ascorbic acid (AA). Based on the above principle, the target CA15-3-triggered immunoassay enriched ALP-catalyzed AAP produces a large amount of AA, resulting in a significant change in the system current signal, thereby realizing the highly sensitive detection of CA15-3. Under the optimal AAP substrate concentration and ALP catalysis time, the Co-NC-SPCE-based electrochemical immunoassay demonstrated a good DPV current for CA15-3 in the assay interval of 1.0 mU/mL to 10,000 mU/mL, with a calculated limit of detection of 0.38 mU/mL. Since Co-NC-SPCE has an excellent DPV current response to AA and employs split-type scheme, the constructed electrochemical immunoassay has the merits of high preciseness and anti-interference, and its clinical diagnostic results are comparable to those of commercial kits.

Asunto(s)

Ácido Ascórbico , Biomarcadores de Tumor , Neoplasias de la Mama , Carbono , Cobalto , Técnicas Electroquímicas , Mucina-1 , Nitrógeno , Humanos , Inmunoensayo/métodos , Neoplasias de la Mama/sangre , Mucina-1/sangre , Biomarcadores de Tumor/sangre , Técnicas Electroquímicas/métodos , Carbono/química , Nitrógeno/química , Cobalto/química , Ácido Ascórbico/química , Ácido Ascórbico/sangre , Ácido Ascórbico/análogos & derivados , Femenino , Límite de Detección , Fosfatasa Alcalina/sangre , Fosfatasa Alcalina/química , Electrodos , Técnicas Biosensibles/métodos

RESUMEN

A label-free optical sandwich immunoassay sensor, utilizing weak value amplification and total internal reflection, was devised for real-time, high-sensitivity analysis and detection of low-concentration targets. 3D printed channels and sodium chloride solution were employed to ensure reproducibility, reliability, and stability of the measurements for calibration. The sandwich structure demonstrated enhanced responsiveness in the proposed optical biosensor through a comparative analysis of the direct assay and sandwich assay for detecting alpha-fetoprotein (AFP) at the same concentration. By optimizing the binding sequences of the coating antibody, target, and detection antibody in the sandwich method, a more suitable sandwich sensing approach based on weak value amplification was achieved. With this approach, the limit of detection (LOD) of 6.29 ng/mL (pM level) for AFP in PBS solution was achieved. AFP testing and regeneration experiments in human serum have proved the feasibility of our methods in detecting complex samples and the reusability of sensing chips. Additionally, the method demonstrated excellent selectivity for unpaired antigens. The efficacy of this methodology was evaluated by simultaneously detecting AFP, carcinoembryonic antigen (CEA), and CA15-3 on a singular sensor chip. In conclusion, the label-free sandwich immunoassay sensing scheme holds promise for advancing the proposed optical sensors based on weak value amplification in early diagnosis and prevention applications. Compared to other biomarker detection methods, it will be easier to promote in practical applications.

Asunto(s)

Técnicas Biosensibles , Antígeno Carcinoembrionario , Límite de Detección , alfa-Fetoproteínas , Técnicas Biosensibles/métodos , alfa-Fetoproteínas/análisis , Humanos , Antígeno Carcinoembrionario/sangre , Antígeno Carcinoembrionario/análisis , Inmunoensayo/métodos , Mucina-1/sangre , Mucina-1/análisis , Anticuerpos Inmovilizados/inmunología , Anticuerpos Inmovilizados/química

RESUMEN

Although circulating tumor cells (CTCs) have demonstrated considerable importance in liquid biopsy, their detection is limited by low concentrations and complex sample components. Herein, we developed a homogeneous, simple, and high-sensitivity strategy targeting breast cancer cells. This method was based on a non-immunological stepwise centrifugation preprocessing approach to isolate CTCs from whole blood. Precise quantification is achieved through the specific binding of aptamers to the overexpressed mucin 1 (MUC1) and human epidermal growth factor receptor 2 (HER2) proteins of breast cancer cells. Subsequently, DNAzyme cleavage and parallel catalytic hairpin assembly (CHA) reactions on the cholesterol-stacking DNA machine were initiated, which opened the hairpin structures T-Hg2+-T and C-Ag+-C, enabling multiple amplifications. This leads to the fluorescence signal reduction from Hg2+-specific carbon dots (CDs) and CdTe quantum dots (QDs) by released ions. This strategy demonstrated a detection performance with a limit of detection (LOD) of 3 cells/mL and a linear range of 5-100 cells/mL. 42 clinical samples have been validated, confirming their consistency with clinical imaging, pathology findings and the folate receptor (FR)-PCR kit results, exhibiting desirable specificity of 100% and sensitivity of 80.6%. These results highlight the promising applicability of our method for diagnosing and monitoring breast cancer.

Asunto(s)

Técnicas Biosensibles , Neoplasias de la Mama , Colesterol , ADN Catalítico , Células Neoplásicas Circulantes , Humanos , Femenino , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/patología , Neoplasias de la Mama/sangre , Técnicas Biosensibles/métodos , ADN Catalítico/química , Biopsia Líquida/métodos , Células Neoplásicas Circulantes/patología , Colesterol/sangre , Colesterol/análisis , Límite de Detección , Puntos Cuánticos/química , Receptor ErbB-2/análisis , Mucina-1/análisis , Mucina-1/sangre , Aptámeros de Nucleótidos/química , Línea Celular Tumoral , Telurio/química , Compuestos de Cadmio/química

RESUMEN

Connective tissue disease-associated interstitial lung disease (CTD-ILD) is an important underlying cause of morbidity and mortality in patients with CTD. Serum Krebs von den Lungen-6 (KL-6) is an immune factor which has been related to the severity of ILD. This systematic review and meta-analysis aimed to evaluate the association between serum KL-6 and mortality of patients with CTD-ILD. Longitudinal studies relevant to the aim of the meta-analysis were retrieved by search of electronic databases including PubMed, Web of Science, and Embase. A random-effects model was used to combine the data by incorporating the influence of between-study heterogeneity. Fifteen cohorts involving 1737 patients with CTD-ILD were included. During a mean follow-up of 35.3 months, 430 (24.8%) patients died. Compared to those with a lower KL-6 at admission, patients with a higher KL-6 were associated with a higher mortality risk during follow-up (risk ratio: 2.18, 95% confidence interval: 1.66 to 2.87, P < 0.001; I2 = 20%). Subgroup analysis showed a significant association in studies from Asian countries, but not in those from non-Asian countries; in studies with cutoff of KL-6 derived in receiver operating characteristic (ROC) curve analysis, but not in those derived from other methods; in studies with multivariate analysis, but not in those with univariate analysis (P for subgroup difference all < 0.05). The association was not significantly affected by different CTDs or methods for measuring serum KL-6. In conclusion, a high serum KL-6 may be a risk factor of increased mortality in patients with CTD-ILD.

Asunto(s)

Enfermedades del Tejido Conjuntivo , Enfermedades Pulmonares Intersticiales , Mucina-1 , Humanos , Enfermedades Pulmonares Intersticiales/mortalidad , Enfermedades Pulmonares Intersticiales/sangre , Mucina-1/sangre , Enfermedades del Tejido Conjuntivo/mortalidad , Enfermedades del Tejido Conjuntivo/complicaciones , Enfermedades del Tejido Conjuntivo/sangre , Biomarcadores/sangre