Systematic Investigation of Key Drivers of Lung Adenocarcinoma: A Focus on Genes, Pathways, and miRNAs

Lung cancer remains a leading cause of cancer-related mortality worldwide, largely due to its asymptomatic progression in early stages and the development of drug resistance. Non-small cell lung cancer (NSCLC) accounts for 80% of all lung cancer cases, and lung adenocarcinoma (LUAD) is the most prevalent subtype. Despite advancements in treatment, the 5-year survival rate for LUAD remains low. A comprehensive literature review across various databases was conducted to curate a robust set of LUAD-associated genes. These genes were used to construct a weighted network based on KEGG pathway similarity, followed by clustering, hub gene detection, and gene ontology analysis. In parallel, a protein-protein interaction (PPI) network and a gene-miRNA regulatory network were established to provide additional layers of molecular insight. Our analysis identified 48 genes as central to LUAD pathogenesis. Several of these genes, along with their corresponding miRNAs, exhibited significant dysregulation in LUAD tissues. The hub genes PIK3CA, BRAF, EGFR, ERBB2, FGFR3, MTOR, and TP53, along with KRAS, MET, and FGFR2, emerged as potential biomarkers. Additionally, miR-17-5p and miR-27a-3p were highlighted as novel biomarker candidates with strong implications in LUAD biology. In conclusion, this study provides a refined list of genes and miRNAs with high relevance for LUAD, alongside key signaling pathways central to disease progression. These findings establish a foundation for future studies and support the development of targeted therapeutic strategies aimed at improving clinical outcomes in LUAD.