Multiomics analysis identifies the prognostic significance and biological roles of the HNRNP family in lung adenocarcinoma.

purposeThe heterogeneous nuclear ribonucleoprotein (HNRNP) family plays pivotal roles in multiple aspects of RNA metabolism. Recent studies suggest that HNRNP dysregulation can promote tumor development. Therefore, this study aims to systematically characterize the expression profiles, immunological associations, and prognostic significance of HNRNP family members in LUAD.

methodsComprehensive transcriptomic and proteomic analyses were conducted using TCGA, GTEx, GEO, and CPTAC LUAD cohorts. Differential expression, immune infiltration, and survival analyses were performed using bioinformatics approaches including ssGSEA, TIDE, and Cox regression modeling. Functional enrichment and alternative splicing profiling were further applied to explore potential mechanisms, with a focus on HNRNPC.

resultsMultiple HNRNP genes were significantly overexpressed in LUAD tissues across datasets. Their expression levels positively correlated with tumor stage, metastasis, recurrence, and TP53 mutation status. High expression of several HNRNPs was associated with poor overall survival, with HNRNPC identified as an independent prognostic indicator in both TCGA and GEO cohorts. Elevated HNRNP expression was linked to reduced immune cell infiltration and lower stromal, immune, and ESTIMATE scores, alongside increased TIDE and Exclusion scores, suggesting immunosuppressive roles in the tumor microenvironment. Functionally, HNRNPC was associated with the activation of cell cycle progression and DNA damage repair. Alternative splicing analysis revealed that HNRNPC predominantly regulates exon skipping events, with enriched downstream pathways involved in chromatin remodeling and transcriptional regulation.

conclusionThis study highlights the critical roles of HNRNP family members in LUAD, identifying HNRNPC as a key prognostic biomarker and potential intervention candidate to improve patient outcomes.