Breast cancer (BRCA) is a complex disease that leads to major mortalities and unsatisfactory clinical outcomes among women worldwide. CKLF-like MARVEL transmembrane domain-containing 7 (CMTM7) is a potential tumor suppressor and regulator of PD-L1, which has been found as a functional signature in considerable oncogenesis, progression, and therapeutic resistance via deletion and downregulation. In this research, triple-negative breast cancer (BRCA), a molecular subtype having a lower response to endocrinotherapy but a higher response to chemotherapy and immunotherapy, showed higher transcriptional levels of CMTM7. Moreover, CMTM7 positively correlated with immunomodulators, tumor-infiltrating immune cells (TIICs), and immune checkpoints in many independent datasets. Furthermore, in an immunotherapy cohort of BRCA, patients with high CMTM7 expression were more sensitive to immunotherapy, and the therapeutic predictive value of CMTM7 is higher than that of PD-1 and PD-L1. To sum up, CMTM7 correlated with an inflamed tumor microenvironment and identified immune-hot tumors, which can be a novel biomarker for the recognition of immunological characteristics and an immunotherapeutic response in BRCA.

Background Proteasome 26S subunit ATPase 2 (PSMC2) is a part of the 19S regulatory complex, which catalyzes the unfolding and transport of substrates into the 20S proteasome. Our previous research demonstrated that PSMC2 participates in the tumorigenesis and progression of pancreatic cancer (PC). However, no systematic analysis has been conducted to conclude its expression pattern and correlation with tumor immunity. Aim To investigate the expression level of PSMC2 in PC, its prognostic value and its relationship with tumor immunity. Methods In numerous public and internal cohorts, the expression, prognostic significance, and immunological connections of PSMC2 in PC were investigated. Additionally, using data from The Cancer Genome Atlas (TCGA), a pan-cancer analysis was carried out to examine PSMC2’s immunological assocaition, and the predictive power of PSMC2 for immunotherapy was also evaluated in numerous public cohorts. Results PSMC2 was overexpressed in tumor tissues and linked to unfavorable prognosis in PC. PSMC2 was not only positively correlated with TIICs, also positively correlated with immune checkpoints in PC. In addition to PC, PSMC2 was expected to be an indicator of high immunogenicity in most cancer types. Importantly, PSMC2 could predict the immunotherapeutic responses in various cancer types, including urothelial carcinoma and breast cancer. Conclusion From PC to pan-cancer analysis, we report that PSMC2 is a novel prognostic biomarker in multiple cancer types. PSMC2 is related to the immuno-hot phenotype and predicts the outcome of immunotherapy. Therefore, the current study emphasizes that cancer patients with high PMSC2 expression should actively receive immunotherapy to improve their prognosis.