Work

Prognostic role and functional impact of cadherin genes in non-small cell lung cancer tumorigenesis: mechanistic insights from in silico and in vitro analyses

Year: 2025

Type: article

Abstract: Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related mortality worldwide, with poor prognosis and limited treatment options for advanced stages. Dysregulation of cadherin expression has been implicated in various cancers, but their exact roles and diagnostic potential of these genes in NSCLC remain unclear. The aim of this study is to investigate the diagnostic and prognostic significance of cadherin family genes (CDH1, CDH2, and CDH3) in NSCLC. This study follows an experimental design, involving both in vitro analyses of cell lines and survival data analysis from public databases. Nine NSCLC cell lines and five normal lung tissue-derived cell lines were cultured and CDH1, CDH2, and CDH3 expression was analyzed via RT-qPCR. Protein expression was validated using the Human Protein Atlas and survival analysis was conducted with the Kaplan-Meier database. Functional roles and regulatory mechanisms of cadherin genes were explored through mutational analysis, PPI networks, and miRNA interactions. The results revealed that all three cadherin genes were significantly upregulated in NSCLC cell lines and tissue samples compared to normal controls. Mutational and copy number variation analyses revealed frequent alterations in CDH2, CDH3, and CDH1 in NSCLC. Additionally, we identified hsa-miR-217, hsa-miR-203a-3p.2, and hsa-miR-6766-3p as potential regulatory miRNAs. The results of functional assays indicate that the silencing of CDH1 and CDH2 inhibits cell proliferation, colony formation, and migration in A549 cells, highlighting their potential roles in promoting tumorigenic and migratory properties in NSCLC. Collectively, our findings suggest that cadherin family genes (CDH1, CDH2, and CDH3) play critical roles in NSCLC tumorigenesis and progression, highlighting their significance as diagnostic markers.

Source: PeerJ

DOI: 10.7717/peerj.19785