Aldahlawi Alia, Basingab Fatemah, Alrahimi Jehan, Zaher Kawther, Pushparaj Peter Natesan, Hassan Mohammed A, Al-Sakkaf Kaltoom
Department of Biological Sciences, Faculty of Sciences, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
Immunology Unit, King Fahad for Medical Research, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
Biomed Rep. 2023 Jul 17;19(2):56. doi: 10.3892/br.2023.1638. eCollection 2023 Aug.
Breast cancer (BC) is the most common cancer in women worldwide, with 2.3 million cases recorded in 2020. Despite improvements in cancer treatment, patients with BC still succumb to the disease, due to regional and distant metastases when diagnosed at later stages. Several immune checkpoint inhibitors have been approved for BC treatment, based on their expression and role in maintaining immunosurveillance against tumors. The present study aimed to evaluate the expression of 12 immune checkpoints in patients with BC, and assess their role as diagnostic and therapeutic markers. Expression levels were measured using reverse transcription-quantitative polymerase chain reaction. Among the 12 immune markers, herpesvirus entry mediator (HVEM) was found to be significantly upregulated in patients with malignant BC compared to non-malignant controls, with a relative fold change (FC) of 1.46 and P=0.012. A similar finding was observed for cytotoxic T-lymphocyte-associated antigen 4 (CTLA4; FC=1.47 and P=0.035). In addition, receiver operating characteristic curve analysis revealed that HVEM expression allowed significant differentiation between groups, with an area under the curve of 0.74 (P=0.013). Upregulation in both HVEM and CTLA4 was revealed to be significantly associated with the human epidermal growth factor receptor-2 (HER2)-enriched phenotype (FC=3.53, P=0.009 and FC=5.98, P=0.002, respectively), while only HVEM was significantly associated with the triple-negative phenotype (FC=2.07, P=0.016). Furthermore, HVEM was significantly higher in patients with grade III tumors (FC=1.88, P=0.025) and negative vascular invasion (FC=1.67, P=0.046) compared with non-malignant controls. Serum protein levels were assessed by multiplex immunoassay, and a significant increase in HVEM was detected in patients with malignant BC compared with that in non-malignant controls (P=0.035). These data indicated that HVEM may serve as a potential biomarker and target for immunotherapy, especially for certain types of BC.
乳腺癌（BC）是全球女性中最常见的癌症，2020年记录了230万例病例。尽管癌症治疗有所改善，但BC患者在晚期被诊断出时，仍会因局部和远处转移而死于该疾病。基于几种免疫检查点抑制剂在维持对肿瘤的免疫监视中的表达和作用，它们已被批准用于BC治疗。本研究旨在评估BC患者中12种免疫检查点的表达，并评估它们作为诊断和治疗标志物的作用。使用逆转录定量聚合酶链反应测量表达水平。在这12种免疫标志物中，发现疱疹病毒进入介质（HVEM）在恶性BC患者中与非恶性对照相比显著上调，相对倍数变化（FC）为1.46，P = 0.012。细胞毒性T淋巴细胞相关抗原4（CTLA4；FC = 1.47，P = 0.035）也有类似发现。此外，受试者工作特征曲线分析显示，HVEM表达能够显著区分不同组，曲线下面积为0.74（P = 0.013）。结果显示，HVEM和CTLA4的上调均与富含人表皮生长因子受体2（HER2）的表型显著相关（分别为FC = 3.53，P = 0.009和FC = 5.98，P =
