https://orcid.org/0000-0002-5848-6440
Abstract
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.
Abbreviation
PC, Pancreatic cancer; PD-1, programmed cell death 1; TME, tumor microenvironment; PSMC2, Proteasome 26S subunit ATPase 2; TCGA, The Cancer Genome Atlas; TIIC, tumor-infiltrating immune cell; IHC, immunohistochemistry; OS, overall survival; PFS, progression free survival; UPS, ubiquitin-proteasome system.
Data Sharing Statement
All data human data used in study is publicly available. Data and materials can be provided upon reasonable request to the corresponding authors.
Ethics Approval and Consent to Participate
Ethical approval (No. YB-M-05-02) for the use of TMA was granted by the Clinical Research Ethics Committee in Outdo Biotech (Shanghai, China).
Author Contributions
All listed authors must have made a significant scientific contribution to the research in the manuscript approved its claims and agreed to be an author. All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.
Disclosure
The authors declare that they have no competing interests in this work.