Systematics investigation of key drivers of lung adenocarcinoma: A focus on genes, pathways, and miRNAs

Abstract

Introduction Lung cancer remain a leading cause of cancer-related death, 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, with lung adenocarcinoma (LUAD) being the most prevalent subtype. Despite advancements in treatment, the 5-year survival rate for LUAD remains low. Therefore, exploring gene networks may reveal novel therapeutic targets and pave the way for improved Method A comprehensive literature review was conducted across various databases containing multi-level genomic information. From this, a robust list of LUAD-related genes was curated. These genes were used to construct a weighted network based on KEGG pathway similarity. The network was subjected to clustering, hub gene detection, and gene ontology analysis. In parallel, a protein-protein interaction (PPI) network was constructed around these genes, which was further enriched with miRNA data to develop a gene-miRNA regulatory network. Results Following our analysis, 48 genes were identified as crucial to LUAD. Many of these genes, along with their corresponding miRNAs, were found to be either upregulated or downregulated in LUAD tissues. The hub genes and miRNAs identified are believed to play key roles in the initiation and progression of LUAD. Our network analysis highlighted PIK3CA, BRAF, EGFR, ERBB2, FGFR3, MTOR, and TP53, along with KRAS, MET, and FGFR2, as potential biomarkers. Additionally, miR-17-5p and miR-27a-3p, which are notably implicated in LUAD, emerged as novel biomarker candidates. Conclusion In conclusion, we employed a combination of bioinformatics techniques and database mining to derive a refined list of genes and miRNAs with high potential for further research in LUAD. We also identified core pathways that play a critical role in LUAD pathogenesis, providing a foundation for future studies aimed at developing more targeted therapeutic approaches.