Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Department of Pathology, National University Hospital, Singapore, Singapore.
Cell Prolif. 2024 Sep;57(9):e13708. doi: 10.1111/cpr.13708. Epub 2024 Jul 9.
This study investigates CD151, a protein linked to cancer progression, in non-small cell lung cancer (NSCLC) patients without epidermal growth factor receptor (EGFR) mutations. These patients often have limited treatment options. The study used retrospective analysis to examine 157 adenocarcinoma biopsy specimens and 199 patient cases from The Cancer Genome Atlas, correlating CD151 expression with patient survival. Cellular studies revealed that CD151 interacts with EGFR, influencing epidermal growth factor (EGF)-induced cell proliferation and the effectiveness of the EGFR inhibitor, erlotinib. A strong association was found between CD151 expression and EGFR mutation status. High CD151 expression in the absence of EGFR mutations is correlated with poorer survival outcomes. Biological assays showed that CD151 colocalizes and associates with EGFR, playing a crucial role in regulating EGF-induced cell proliferation via the AKT and ERK1/2 pathways. Importantly, CD151 expression was found to influence the anti-proliferative effects of the EGFR tyrosine kinase inhibitor, erlotinib. High CD151 expression, in the absence of EGFR mutations, was associated with poorer survival outcomes. It could serve as a potential prognostic marker and influence cellular responses to EGFR-targeted treatments. This study highlights CD151 as a potential novel target for therapeutic intervention in NSCLC, especially in populations lacking EGFR mutations.
本研究调查了非小细胞肺癌(NSCLC)患者中与癌症进展相关的蛋白 CD151,这些患者没有表皮生长因子受体(EGFR)突变,他们通常治疗选择有限。该研究使用回顾性分析,检查了来自癌症基因组图谱的 157 个腺癌活检标本和 199 例患者病例,将 CD151 表达与患者生存相关联。细胞研究表明,CD151 与 EGFR 相互作用,影响表皮生长因子(EGF)诱导的细胞增殖和 EGFR 抑制剂厄洛替尼的效果。发现 CD151 表达与 EGFR 突变状态之间存在强烈关联。在没有 EGFR 突变的情况下,CD151 表达较高与生存结果较差相关。生物测定表明,CD151 与 EGFR 共定位和关联,通过 AKT 和 ERK1/2 通路在调节 EGF 诱导的细胞增殖中发挥关键作用。重要的是,发现 CD151 表达会影响 EGFR 酪氨酸激酶抑制剂厄洛替尼的抗增殖作用。在没有 EGFR 突变的情况下,CD151 表达较高与生存结果较差相关。它可以作为一个潜在的预后标志物,并影响细胞对 EGFR 靶向治疗的反应。这项研究强调了 CD151 作为 NSCLC 治疗干预的潜在新靶点,特别是在缺乏 EGFR 突变的人群中。