Impact of CD151 overexpression on prognosis and therapy in non-small cell lung cancer patients lacking EGFR mutations

Cell Prolif. 2024 Sep;57(9):e13708. doi: 10.1111/cpr.13708. Epub 2024 Jul 9.

Abstract

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.

MeSH terms

  • Aged
  • Carcinoma, Non-Small-Cell Lung* / drug therapy
  • Carcinoma, Non-Small-Cell Lung* / genetics
  • Carcinoma, Non-Small-Cell Lung* / metabolism
  • Carcinoma, Non-Small-Cell Lung* / pathology
  • Cell Line, Tumor
  • Cell Proliferation* / drug effects
  • Cell Proliferation* / genetics
  • ErbB Receptors* / antagonists & inhibitors
  • ErbB Receptors* / genetics
  • ErbB Receptors* / metabolism
  • Erlotinib Hydrochloride* / pharmacology
  • Erlotinib Hydrochloride* / therapeutic use
  • Female
  • Humans
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / genetics
  • Lung Neoplasms* / metabolism
  • Lung Neoplasms* / pathology
  • Male
  • Middle Aged
  • Mutation*
  • Prognosis
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use
  • Retrospective Studies
  • Tetraspanin 24* / genetics
  • Tetraspanin 24* / metabolism

Substances

  • Tetraspanin 24
  • ErbB Receptors
  • CD151 protein, human
  • Erlotinib Hydrochloride
  • EGFR protein, human
  • Protein Kinase Inhibitors