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. 2023 Aug 9:16:747-758.
doi: 10.2147/PGPM.S418533. eCollection 2023.

PSMC2 is a Novel Prognostic Biomarker and Predicts Immunotherapeutic Responses: From Pancreatic Cancer to Pan-Cancer

Wei Huang #  1 , Zhengtao Qian #  2 , Yuxin Shi #  1   3 , Zheming Zhang  3 , Rui Hou  1   3 , Jie Mei  1   3 , Junying Xu  1 , Junli Ding  1
Affiliations

PSMC2 is a Novel Prognostic Biomarker and Predicts Immunotherapeutic Responses: From Pancreatic Cancer to Pan-Cancer

Wei Huang et al. Pharmgenomics Pers Med. .

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.

Keywords: PSMC2; bioinformatics; biomarker; pancreatic cancer; tumor immunity.

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Conflict of interest statement

The authors declare that they have no competing interests in this work.

Figures

Figure 1
Figure 1
Expression and prognostic values of PSMC2 in pancreatic cancer. (A) Expression of PSMC2 in normal and tumor tissues. Data were obtained from the GEPIA database. (B) Expression of PSMC2 in normal and tumor tissues. Data were obtained from the GSE28735 database. (C) Expression of PSMC2 in normal and tumor tissues. Data were obtained from the GSE62454 database. (D) Representative images uncovering PSMC2 expression in normal and tumor tissues using anti-PSMC2 staining and semi-quantitative analysis. (E) Kaplan-Meier analysis showed survival curves of overall survival (OS) in patients with low and high PSMC2 expression in pancreatic cancer.
Figure 2
Figure 2
Co-expressed genes and enrichment analysis of PSMC2 in pancreatic cancer. (A) The global PSMC2 highly associated genes identified by Pearson test in pancreatic cancer cohort. (B) Heat maps showing top 50 genes positively and negatively associated with PSMC2 in pancreatic cancer. (C) Enrichment analysis of the positively correlated genes in the term of KEGG analysis. (D) Enrichment analysis of the negatively correlated genes in the term of KEGG analysis.
Figure 3
Figure 3
Association between PSCM2 expression and TME features in pancreatic cancer. (A) PSCM2 expression in pancreatic cancer tissues is positively correlated with infiltration levels of B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and DCs. (B) PSCM2 expression in pancreatic cancer tissues is positively correlated with immune checkpoints expression, including PD-L1, PD-L2, LAG3, CTLA4, PVR, and HAVCR2. (C) Representative images uncovering low and high PSMC2 and PD-L1 expressions in pancreatic cancer using anti-PSMC2 and anti-PD-L1 staining. (D) Correlation between PSMC2 and PD-L1 expressions in pancreatic cancer tissues.
Figure 4
Figure 4
Expression and prognostic values of PSMC2 in pan-cancer. (A) The level of PSMC2 expression in different tumor types from the TCGA and the GTEx database. Note: “*” indicates statistical significance. (B and C) Kaplan-Meier analysis showed survival curves of OS and progression free survival (PFS) in patients with low and high PSMC2 expression in pan-cancer. (D and E) Forest plot showing the prognostic values of PSMC2 in terms of OS and PFS in different cancer types.
Figure 5
Figure 5
Immuno-correlations of PSMC2 in pan-cancer. (A) Correlations between PSMC2 and 150 immunomodulators (MHC, receptors, chemokines, immunoinhibitors, and immunostimulators) in pan-cancer.
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