PSMB7 is associated with DNA damage repair and immune microenvironment features and serves as a prognostic biomarker

The clinical significance and biological roles of PSMB7 in lung adenocarcinoma (LUAD) remain incompletely understood. This study aimed to comprehensively characterize PSMB7 expression, prognostic value, epigenetic regulation, immune associations, and in vitro functions in LUAD.

PSMB7 expression, clinicopathological associations, prognostic value, epigenetic regulation, co-expression networks, functional pathways, and relationships with the tumor immune microenvironment were systematically evaluated across multiple datasets. External validation was performed in the GSE31210 cohort. Prognostic nomogram performance was additionally evaluated using Harrell's concordance index (C-index) and time-dependent decision curve analysis (DCA). In vitro experiments, including Western blotting, CCK-8 assays, and flow cytometry, were conducted to assess the effects of PSMB7 on cell proliferation and irradiation-induced apoptosis in LUAD cell lines.

PSMB7 was significantly upregulated in LUAD and was associated with advanced pathological T and N stages and overall clinical stage. ROC analysis indicated that PSMB7 showed potential discriminatory ability between LUAD and normal lung tissues. High PSMB7 expression independently predicted unfavorable outcomes across multiple prognostic endpoints. Nomogram evaluation using calibration, C-index, and DCA provided complementary evidence for prognostic performance. PSMB7 hypomethylation was associated with poorer survival. PSMB7 expression was positively correlated with DNA mismatch repair genes, RNA modification regulators, and malignant tumor phenotypes. GSEA showed significant enrichment of oncogenic, cell-cycle, metabolic, DNA-repair, and stress-response pathways. In addition, PSMB7 expression was strongly associated with immune scores, immune-cell infiltration, and the expression of immune modulators, MHC molecules, chemokines, and chemokine receptors in LUAD. In vitro, PSMB7 knockdown suppressed cell proliferation and enhanced irradiation-induced apoptosis, whereas PSMB7 overexpression promoted proliferation and reduced apoptosis after irradiation.

PSMB7 is a candidate independent prognostic biomarker in LUAD and is associated with malignant progression, immune microenvironment features, and cellular responses to irradiation consistent with a potential role in radioresistance. These findings support PSMB7 as a potential therapeutic target in LUAD.