Comprehensive pan-cancer multi-omics analysis of PSMB7 reveals its prognostic significance and oncogenic role with experimental validation in lung and gastric cancers

Objective PSMB7 is a key component of the ATP-dependent proteolytic complex and plays an essential role in cellular protein degradation. While emerging evidence suggests its involvement in cancer, its roles in tumor progression, prognosis, and diagnosis remain largely uncharacterized. This study aimed to investigate the expression profile of PSMB7 and its association with clinical outcomes and tumor biology across multiple cancer types. Methods We conducted a comprehensive bioinformatic analysis using pan-cancer data from The Cancer Genome Atlas (TCGA). Gene set enrichment analysis (GSEA) and protein–protein interaction (PPI) network construction were performed to explore the functional roles of PSMB7. The correlation between PSMB7 expression and tumor-infiltrating immune cells was assessed using CIBERSORT, IPS, and QUANTISEQ. Single-cell RNA sequencing data were analyzed to determine PSMB7 expression across distinct cell populations. Furthermore, siRNA-mediated knockdown of PSMB7 was carried out in A549 and AGS cells. Functional assays—including Western blotting, colony formation, and Transwell migration/invasion—were used to assess phenotypic effects. Subcutaneous xenograft models of lung and gastric cancer were established in nude mice to evaluate the in vivo impact of PSMB7 depletion on tumor growth. Results PSMB7 was significantly upregulated in multiple cancer types compared to adjacent normal tissues. Its expression was positively associated with clinical and molecular features such as stemness scores, stromal and immune scores, tumor mutational burden (TMB), microsatellite instability (MSI), and drug sensitivity. Notably, high PSMB7 expression correlated with altered sensitivity to several chemotherapeutic agents. Functionally, PSMB7 knockdown markedly inhibited cancer cell proliferation, migration, and invasion in vitro, and suppressed tumor growth in vivo. Conclusion PSMB7 is broadly overexpressed in human cancers and is significantly associated with key prognostic indicators, immune cell infiltration, and therapeutic responsiveness. These findings highlight the clinical relevance of PSMB7 as a potential biomarker and therapeutic target, paving the way for its application in personalized cancer treatment strategies.