Habel Azza, Weili Xu, Hadj Ahmed Mariem, Stayoussef Mouna, Bouaziz Hanen, Ayadi Mouna, Mezlini Amel, Larbi Anis, Yaacoubi-Loueslati Basma
Laboratory of Mycology, Pathologies, and Biomarkers (LR16ES05), Faculty of Sciences of Tunis, University of Tunis El Manar, Tunis, Tunisia.
Singapore Immunology Network, Agency for Science Technology and Research (A*STAR), Singapore, Singapore.
Int J Biol Markers. 2023 Dec;38(3-4):203-213. doi: 10.1177/03936155231186163. Epub 2023 Jul 30.
Epithelial ovarian cancer (EOC) is the leading cause of death associated with gynecologic tumors. EOC is asymptomatic in early stages, so most patients are not diagnosed until late stages, highlighting the need to develop new diagnostic biomarkers. Mediators of the tumoral microenvironment may influence EOC progression and resistance to treatment.
To analyze immune checkpoints to evaluate them as theranostic biomarkers for EOC.
Serum levels of 16 immune checkpoints were determined in EOC patients and healthy controls using the MILLIPLEX MAP Human Immuno-Oncology Checkpoint Protein Magnetic Bead Panel.
Seven receptors: BTLA, CD40, CD80/B7-1, GITRL, LAG-3, TIM-3, TLR-2 are differentially expressed between EOC and healthy controls. Serum levels of immune checkpoints in EOC patients are positively significantly correlated with levels of their ligands, with a higher significant correlation between CD80 and CTLA4 than between CD28 and CD80. Four receptors, CD40, HVEM, PD-1, and PD-L1, are positively associated with the development of resistance to Taxol-platinum-based chemotherapy. All of them have an acceptable area under the curve (>0.7).
This study has yielded a first panel of seven immune checkpoints (BTLA, CD40, CD80/B7-1, GITRL, LAG-3, TIM-3, TLR-2) associated with a higher risk of EOC and a second panel of four immune checkpoints (CD40, HVEM, PD-1, PD-L1) that may help physicians to identify EOC patients who are at high risk of developing resistance to EOC chemotherapy.
上皮性卵巢癌（EOC）是妇科肿瘤相关死亡的主要原因。EOC在早期无症状，因此大多数患者直到晚期才被诊断出来，这凸显了开发新诊断生物标志物的必要性。肿瘤微环境的介质可能影响EOC的进展和对治疗的耐药性。
分析免疫检查点，以评估它们作为EOC的治疗诊断生物标志物。
使用MILLIPLEX MAP人免疫肿瘤学检查点蛋白磁珠板测定EOC患者和健康对照者血清中16种免疫检查点的水平。
七种受体：BTLA、CD40、CD80/B7-1、GITRL、LAG-3、TIM-3、TLR-2在EOC患者和健康对照者之间存在差异表达。EOC患者免疫检查点的血清水平与其配体水平呈显著正相关，CD80与CTLA4之间的相关性高于CD28与CD80之间的相关性。四种受体，CD40、HVEM、PD-1和PD-L1，与对基于紫杉醇-铂的化疗的耐药性发展呈正相关。它们的曲线下面积均可接受（>0.7）。
本研究得出了与EOC风险较高相关联的首批七种免疫检查点（BTLA、CD40、CD80/B7-1、GITRL、LAG-3、TIM-3、TLR-2），以及可能有助于医生识别有EOC化疗耐药高风险的EOC患者的第二批四种免疫检查点（CD40、HVEM、PD-1、PD-L1）。
