Abstract
Lung adenocarcinoma (LUAD) is one of the most prevalent and lethal cancers worldwide, signifying a critical need for improved prognostic tools. A growing number of studies have highlighted the role of microRNAs (miRNAs) and their regulatory functions in tumorigenesis and cancer progression. In this context, we performed an extensive analysis of bulk RNA- and miRNA-sequencing to identify LUAD-associated prognostic genes. A risk score system based on 11 miRNA-regulated and surface-protein genes was developed, which was later validated by internally and externally using the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), respectively. Further single-cell RNA sequencing analysis revealed significant interactions between various cellular subpopulations within the tumor microenvironment, with the most pronounced differences observed between endothelial and epithelial cells. The mutational analysis highlighted TP53 as a key signaling pathway associated with the risk score. The study underscores that immune suppression, indicated by a positive association with regulatory T cells (Tregs) and an inverse correlation with M1-type macrophages, is prevalent in high-risk LUAD patients. These findings provide a promising prognostic tool for clinical outcomes of LUAD patients, facilitating future development of therapeutic strategies and enhancing our understanding of the regulatory function of miRNAs in LUAD.