CD168 in lung adenocarcinoma: prognostic relevance, immune feature associations, and MAPK/ERK pathway enrichment

Lung adenocarcinoma (LUAD), the predominant non-small cell lung cancer (NSCLC) subtype, faces major clinical challenges including poor prognosis and acquired drug resistance. This study integrates multi-omics analyses with in vitro functional validation experiments to systematically elucidate the molecular regulatory mechanisms of hyaluronan receptor (RHAMM/CD168) in LUAD development and its potential clinical translational value. Bioinformatics analysis based on public databases such as TCGA and GEO revealed that CD168 mRNA expression was significantly higher in LUAD tumor tissues compared to adjacent normal tissues. Kaplan-Meier survival analysis and multivariable Cox regression models confirmed that high CD168 expression was independently associated with significantly shorter overall survival (OS) and progression-free survival (PFS) after adjusting for confounding factors such as age, gender, and clinical stage. Moreover, high CD168 expression correlated with altered immune cell infiltration patterns and changes in immune checkpoint molecule expression, suggesting that CD168 may play a crucial role in modulating the immune-suppressive tumor microenvironment and affecting responses to immunotherapy. Functional experiments demonstrated that silencing CD168 significantly inhibited cell proliferation, migration, and invasion in LUAD cell lines (A549 and H1299), and promoted apoptosis, confirming its oncogenic function. Bioinformatics analysis constructed the "lncRNA (CYTOR)-miRNA (hsa-let-7c-5p)-CD168" regulatory axis, wherein CYTOR may function as a ceRNA to sequester hsa-let-7c-5p, thereby alleviating miRNA-mediated suppression of CD168. Furthermore, Western blot analysis revealed that silencing CD168 decreased the phosphorylation levels of ERK and MEK, suggesting that CD168 promotes LUAD progression in association with MAPK/ERK signaling pathway activity. In summary, CD168 may promote LUAD progression by reshaping the immunosuppressive microenvironment and enhancing malignant behavior, establishing it as a prognostic biomarker and a potential therapeutic target, particularly for immunotherapy combinations.