The Clinicopathological and Prognostic Significance of the Expression of PD-L1 and MET Genes in Breast Cancer: Potential Therapeutic Targets.

IF 2.3 4区医学 Q3 ONCOLOGY

Current cancer drug targets Pub Date : 2024-10-10 DOI:10.2174/0115680096333231240902070108

Muhsen Al-Diabat, Nehad M Ayoub, Laith Al-Eitan, Moath Alshorman, Aymen Shatnawi

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引用次数: 0

Abstract

Introduction: The heterogeneity of breast cancer requires exploring novel prognostic biomarkers as well as therapeutic targets for the treatment of the disease.

Methods: 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.

Results: 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.

Conclusion: 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.

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乳腺癌中 PD-L1 和 MET 基因表达的临床病理和预后意义：潜在的治疗靶点。

简介：乳腺癌的异质性要求探索新的预后生物标志物和治疗目标：乳腺癌的异质性要求探索新的预后生物标志物和治疗靶点：方法：利用METABRIC数据集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的肿瘤临床病理特征和总生存期的关系：PD-L1和MET基因的表达与诺丁汉预后指数（NPI）呈正相关（P=0.003和P<0.001）。这两个基因的表达与管腔A型和管腔B型肿瘤呈反向相关（分别为r= - 0.089，p= 0.021和r= - 0.116，p= 0.013）。激素受体阴性和 HER2 阳性肿瘤的 PD-L1 mRNA 水平明显更高。在激素受体阴性、HER2富集和非腔隙性乳腺癌中，MET mRNA表达水平明显较高。PD-L1/MET双高表达与患者诊断时年龄较小、NPI评分较高、肿瘤较大、晚期、高级别、激素受体阴性、HER2阳性和非腔隙性肿瘤有关。在这项分析中，没有一个基因或其双重表达状态与总生存率有明显相关性：结论：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较差的预后明显相关。使用针对 PD-L1 和 MET 的联合用药方案进行进一步研究非常重要，尤其是在这两种蛋白表达水平较高的乳腺肿瘤中。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Current cancer drug targets 医学-肿瘤学

CiteScore

5.40

自引率

0.00%

发文量

105

审稿时长

1 months

期刊介绍： Current Cancer Drug Targets aims to cover all the latest and outstanding developments on the medicinal chemistry, pharmacology, molecular biology, genomics and biochemistry of contemporary molecular drug targets involved in cancer, e.g. disease specific proteins, receptors, enzymes and genes. Current Cancer Drug Targets publishes original research articles, letters, reviews / mini-reviews, drug clinical trial studies and guest edited thematic issues written by leaders in the field covering a range of current topics on drug targets involved in cancer. As the discovery, identification, characterization and validation of novel human drug targets for anti-cancer drug discovery continues to grow; this journal has become essential reading for all pharmaceutical scientists involved in drug discovery and development.