Identification of key protein-coding genes, lncRNAs and their regulatory network associated with the progression of lung adenocarcinoma in humans

Abstract

Lung adenocarcinoma (LUAD) is an aggressive subtype of non-small cell lung cancer (NSCLC) known for its high propensity for early metastasis and rapid progression, often leading to late-stage diagnosis and poor prognosis. This cancer type frequently spreads to distant organs, including the brain, liver, and bones, contributing to its high mortality rate among lung cancer subtypes. Therefore, effective strategies need to be developed for early detection and prognosis of LUAD. Transcriptomic advancements have helped in better prognosis by analyzing the complex interplay among protein-coding and non-coding genes across various cancers. However, the regulatory mechanisms and the interactions between the coding and non-coding elements involved in LUAD progression is poorly understood. In this quest, we used weighted gene co-expression network analysis (WGCNA) approach on RNA-Seq data and identified a set of protein-coding genes (PCGs) and lncRNAs that are crucial for the development of LUAD. Further, we derived the networks of PCGs with lncRNAs at the mRNA (i.e., transcriptional) and protein (i.e., post-transcriptional) levels. Our analysis revealed 405 PCGs as the candidate biomarkers among which ADAMTS8, PECAM1, RGCC, and TCF21 were detected as key PCGs. Gene ontology and pathway analysis suggested angiogenesis as the crucial pathway regulated by the candidate biomarkers. BANCR was the only lncRNA among those analyzed that showed both differential expression in tumor tissues and a significant association with better survival, making it a promising candidate for further investigation as a prognostic biomarker in LUAD. Further, we identified MALAT1-TCF21-NORAD-SELP-BANCR-KLF2, as the key regulatory mechanism through which BANCR might be regulating the LUAD progression.