Al-Diabat Muhsen, Ayoub Nehad M, Al-Eitan Laith, Alshorman Moath, Shatnawi Aymen
Department of Biotechnology and Genetic Engineering, Faculty of Science and Arts, Jordan University of Science and Technology, P.O. Box: 3030, Irbid, 22110, Jordan.
Department of Clinical Pharmacy, Faculty of Pharmacy, Jordan University of Science and Technology, P.O. Box: 3030, Irbid, 22110, Jordan.
Curr Cancer Drug Targets. 2024 Oct 10. doi: 10.2174/0115680096333231240902070108.
The heterogeneity of breast cancer requires exploring novel prognostic biomarkers as well as therapeutic targets for the treatment of the disease.
The METABRIC dataset was used to describe the gene expression of the programmed death-ligand 1 (PD-L1) and the hepatocyte growth factor receptor (MET) and their association with the tumor clinicopathologic characteristics and overall survival in breast cancer.
The expression of the PD-L1 and MET genes correlated positively with the Nottingham Prognostic Index (NPI) (p=0.003 and p < 0.001, respectively). The expression of the two genes correlated inversely with luminal A and luminal B tumors (r= - 0.089, p= 0.021 and r= - 0.116, p= 0.013, respectively). The PD-L1 mRNA levels were significantly higher in hormone receptor-negative and HER2-positive tumors. MET mRNA expression levels were significantly higher in hormone receptor-negative, HER2-enriched, and non-luminal breast cancers. The PD-L1/MET double-high expression was associated with younger age of patients at diagnosis, higher NPI scores, larger tumors, advanced stage, high-grade, hormone receptor-negativity, HER2-positivity, and non-luminal tumors. None of the genes or their double expression status was significantly associated with overall survival in this analysis.
The expression of the PD-L1 and MET genes is remarkably associated with worse tumor clinicopathologic features and poor prognosis in patients with breast cancer. Further investigations using combination drug regimens targeting PD-L1 and MET are important, particularly in breast tumors expressing high levels of both proteins.
乳腺癌的异质性需要探索新的预后生物标志物以及该疾病治疗的靶点。
使用METABRIC数据集来描述程序性死亡配体1（PD-L1）和肝细胞生长因子受体（MET）的基因表达及其与乳腺癌肿瘤临床病理特征和总生存期的关联。
PD-L1和MET基因的表达与诺丁汉预后指数（NPI）呈正相关（分别为p = 0.003和p < 0.001）。这两个基因的表达与管腔A型和管腔B型肿瘤呈负相关（分别为r = - 0.089，p = 0.021和r = - 0.116，p = 0.013）。在激素受体阴性和HER2阳性肿瘤中，PD-L1 mRNA水平显著更高。在激素受体阴性、HER2富集和非管腔型乳腺癌中，MET mRNA表达水平显著更高。PD-L1/MET双高表达与诊断时患者年龄较小、NPI评分较高、肿瘤较大、分期较晚、高级别、激素受体阴性、HER2阳性和非管腔型肿瘤相关。在此分析中，没有一个基因或其双表达状态与总生存期显著相关。
PD-L1和MET基因的表达与乳腺癌患者较差的肿瘤临床病理特征和不良预后显著相关。使用针对PD-L1和MET的联合药物方案进行进一步研究很重要，特别是在两种蛋白均高表达的乳腺肿瘤中。
