Espinoza-de-León Gabriela Nohemi, Aguilar-Lemarroy Adriana, Vega-Magaña Alejandra Natali, Pereira-Suarez Ana Laura, Muñoz-Valle José Francisco, Villegas-Pacheco Raquel, Jave-Suárez Luis Felipe, García-Chagollán Mariel
Instituto de Investigación en Ciencias Biomédicas, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Mexico.
División de Inmunología, Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social, Guadalajara 44340, Mexico.
Diagnostics (Basel). 2025 Aug 12;15(16):2019. doi: 10.3390/diagnostics15162019.
Serum biomarkers such as CA-125 and HE4, along with the ROMA score, (which integrates both markers) are widely used to distinguish between benign and malignant ovarian tumors. In ovarian cancer, chronic exposure to tumor-associated antigens (TAAs), such as CA-125 and HE4, can lead to T cell exhaustion and senescence, thereby facilitating immune evasion. This study aimed to evaluate exhausted and senescent T cells in the peripheral blood of patients with benign or malignant ovarian tumors, and compare these findings to those of healthy donors, and assess their correlation with the ROMA score. The expression of senescent and exhaustion markers was evaluated on peripheral CD4 T cells from patients with benign and malignant ovarian tumors, as well as healthy donors. Multicolor flow cytometry was performed to evaluate the expression of CTLA-4, PD-1, Tim3, CD28, CD57, and CD27. PD1Tim3CD4 expression was significantly higher in the malignant group compared to both the benign group ( = 0.05) and healthy donors ( = 0.015). A positive and significant correlation was observed between ROMA and PD-1Tim3 T cells (r = 0.44, 0.0006). The confusion matrix demonstrated good classification accuracy, and in the ROC analysis, the combination of ROMA and PD-1Tim3 yielded the highest Youden Index (0.75) and superior specificity (88.8%) compared to ROMA alone, albeit with a slight reduction in sensitivity (86.9% vs. 91.3%). A nomogram integrating ROMA and PD-1Tim3 exhibited strong predictive performance, with a concordance index (C-index) of 0.91. The combination of the ROMA score with the expression of PD-1 and Tim-3 in CD4 T cells creates a simple yet highly effective model to differentiate between benign and malignant ovarian tumors.
血清生物标志物如CA - 125和HE4，以及ROMA评分（整合了这两种标志物）被广泛用于区分良性和恶性卵巢肿瘤。在卵巢癌中，长期暴露于肿瘤相关抗原（TAA），如CA - 125和HE4，可导致T细胞耗竭和衰老，从而促进免疫逃逸。本研究旨在评估良性或恶性卵巢肿瘤患者外周血中耗竭和衰老的T细胞，并将这些结果与健康供体的结果进行比较，同时评估它们与ROMA评分的相关性。对良性和恶性卵巢肿瘤患者以及健康供体的外周血CD4 T细胞进行衰老和耗竭标志物表达评估。采用多色流式细胞术评估CTLA - 4、PD - 1、Tim3、CD28、CD57和CD27的表达。与良性组（P = 0.05）和健康供体（P = 0.015）相比，恶性组中PD1Tim3CD4表达显著更高。观察到ROMA与PD - 1Tim3 T细胞之间存在正相关且具有统计学意义（r = 0.44，P = 0.0006）。混淆矩阵显示出良好的分类准确性，在ROC分析中，与单独的ROMA相比，ROMA与PD - 1Tim3的组合产生了最高的约登指数（0.75）和更高的特异性（88.8%），尽管敏感性略有降低（86.9%对91.3%）。整合ROMA和PD - 1Tim3的列线图表现出强大的预测性能，一致性指数（C指数）为0.91。ROMA评分与CD4 T细胞中PD - 1和Tim - 3表达的组合创建了一个简单而高效的模型，用于区分良性和恶性卵巢肿瘤。
