Comprehensive Bioinformatics Analysis of Differential Gene Expression Differences between Lung Adenocarcinoma and Lung Squamous Cell Carcinoma.

Abstract

Lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) are the two most prevalent histological subtypes of non-small cell lung cancer (NSCLC), each of which exhibits distinct molecular characteristics and requires subtype-specific treatment strategies. This study aimed to comprehensively analyze the differential gene expression profiles between LUAD and LUSC to identify subtype-specific biomarkers and pathogenic pathways. Using RNA-seq data from The Cancer Genome Atlas (TCGA), this study performed differential gene expression analysis with DESeq2, disease-free survival analysis via GEPIA, and pathway enrichment analysis using Enrichr with the KEGG 2021 Human database. A total of 29,052 and 28,866 significant differentially expressed genes (DEGs) were identified in LUAD and LUSC respectively. Key up-regulated genes in LUAD, including FAM83A and FAM83A-AS1, were significantly associated with poor disease-free survival (HR = 1.5, p = 0.0048; HR = 1.6, p = 0.0024), while down-regulated PECAM1 showed protective effects (HR = 0.71, p = 0.03). Pathway analysis revealed significant dysregulation of the cell cycle pathway in both subtypes, with LUAD showing stronger association. The DNA replication pathway was notably prominent in LUSC, while a unique malaria pathway was identified in LUAD. The research findings underscore the molecular heterogeneity between LUAD and LUSC, highlighting potential prognostic biomarkers like FAM83A and subtype-specific pathogenic pathways, which could inform the development of precise therapeutic interventions between LUAD and LUSC.