Vardas Vasileios, Tolios Anastasios, Christopoulou Athina, Georgoulias Vassilis, Xagara Anastasia, Koinis Filippos, Kotsakis Athanasios, Kallergi Galatea
Laboratory of Biochemistry/Metastatic Signaling, Section of Genetics, Cell Biology and Development, Department of Biology, University of Patras, GR-26504 Patras, Greece.
Oncology Unit, ST Andrews General Hospital of Patras, GR-26332 Patras, Greece.
Cancers (Basel). 2023 Mar 25;15(7):1974. doi: 10.3390/cancers15071974.
Triple negative breast cancer (TNBC) is the most aggressive breast cancer subtype. There are few targeted therapies for these patients, leading to an unmet need for new biomarkers. The present study aimed to investigate the expression of PD-L1, CTLA-4, GLU, and VIM in CTCs of TNBC patients. Ninety-five patients were enrolled in this study: sixty-four TNBC and thirty-one luminal. Of these patients, 60 were in the early stage, while 35 had metastatic disease. Protein expression was identified by immunofluorescence staining experiments and VyCAP analysis. All the examined proteins were upregulated in TNBC patients. The expression of the GLUVIMCK phenotype was higher (50%) in metastatic TNBC compared to early TNBC patients (17%) ( = 0.005). Among all the BC patients, a significant correlation was found between PD-L1CD45CK and CTLA-4CD45CK phenotypes (Spearman test, = 0.024), implying an important role of dual inhibition in BC. Finally, the phenotypes GLUVIMCK and PD-L1CD45CK were associated with shorter OS in TNBC patients (OS: log-rank = 0.048, HR = 2.9, OS: log-rank < 0.001, HR = 8.7, respectively). Thus, PD-L1, CTLA-4, GLU, and VIM constitute significant biomarkers in TNBC associated with patients' outcome, providing new therapeutic targets for this difficult breast cancer subtype.
三阴性乳腺癌（TNBC）是最具侵袭性的乳腺癌亚型。针对这些患者的靶向治疗方法很少，导致对新生物标志物的需求未得到满足。本研究旨在调查TNBC患者循环肿瘤细胞（CTC）中程序性死亡受体配体1（PD-L1）、细胞毒性T淋巴细胞相关蛋白4（CTLA-4）、波形蛋白（VIM）和谷氨酸（GLU）的表达情况。95名患者纳入本研究：64例TNBC患者和31例管腔型患者。在这些患者中，60例处于早期，35例有转移性疾病。通过免疫荧光染色实验和VyCAP分析鉴定蛋白表达。所有检测的蛋白在TNBC患者中均上调。与早期TNBC患者（17%）相比，转移性TNBC患者中GLUVIMCK表型的表达更高（50%）（P = 0.005）。在所有乳腺癌患者中，发现PD-L1CD45CK和CTLA-4CD45CK表型之间存在显著相关性（Spearman检验，P = 0.024），这意味着双重抑制在乳腺癌中起重要作用。最后，GLUVIMCK和PD-L1CD45CK表型与TNBC患者较短的总生存期相关（总生存期：对数秩检验P = 0.048，风险比[HR]=2.9；总生存期：对数秩检验P<0.001，HR = 8.7）。因此，PD-L1、CTLA-4、GLU和VIM是TNBC中与患者预后相关的重要生物标志物，为这种难治性乳腺癌亚型提供了新的治疗靶点。
