Comprehensive analysis of PTPN gene family revealing PTPN7 as a novel biomarker for immuno-hot tumors in breast cancer

Fengxu Wang; Xuehai Wang; Lei Liu; Siyuan Deng; Wenqian Ji; Yang Liu; Xiangdong Wang; Rui Wang; Xinyuan Zhao; Erli Gao

doi:10.3389/fgene.2022.981603

Comprehensive analysis of PTPN gene family revealing PTPN7 as a novel biomarker for immuno-hot tumors in breast cancer

Front Genet. 2022 Sep 26:13:981603. doi: 10.3389/fgene.2022.981603. eCollection 2022.

Authors

Fengxu Wang¹, Xuehai Wang¹, Lei Liu², Siyuan Deng¹, Wenqian Ji³, Yang Liu¹, Xiangdong Wang¹, Rui Wang¹, Xinyuan Zhao¹, Erli Gao⁴

Affiliations

¹ Department of Occupational Medicine and Environmental Toxicology, Nantong Key Laboratory of Environmental Toxicology, School of Public Health, Nantong University, Nantong, China.
² Department of Pathology, Affiliated Hospital of Nantong University, Nantong, China.
³ College of International Studies, Southwest University, Chongqing, China.
⁴ Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China.

Abstract

Background: The non-receptor protein tyrosine phosphatase (PTPN) gene family has been considered to be involved in the oncogenesis and development of multiple cancers. However, its prognostic utility and immunological relevance in breast cancer (BrCa) have not been clarified. Methods: A transcriptional level interpretation of the expressions and prognostic values was analyzed using the data from The Cancer Genome Atlas (TCGA) cohort. In addition, GO and DAVID pinpoint the functional enrichment of PTPNs. Moreover, the immune correlations of PTPN7 in BrCa and pan-cancer were further investigated based on the TCGA cohort and were testified using the in-house and the Gene Expression Omnibus (GEO) cohorts. Results: For systematic analysis of the PTPN family, we found that the expression levels of PTPN1, PTPN6, PTPN7, PTPN18, PTPN20, and PTPN22 was promoted in tumor tissues while comparing with paraneoplastic tissues during our study. We further investigated their functions and protein-protein interactions (PPI), and these results strongly suggested that PTPN family was associated with protein dephosphorylation. Next, we performed an immunological relevance analysis and found that PTPN7 was correlated with immune infiltration, suggesting a stronger association of PTPN7 with immuno-hot tumors in BrCa. In addition, results from the in-house cohort confirmed the positive correlation between PTPN7 and PD-L1. The pan-cancer analysis revealed that PTPN7 was related to PD-L1 and CTLA-4 expression in almost all cancer types. Finally, the predictive value of PTPN7 for immunotherapy was significant in two independent GEO cohorts. Conclusion: In conclusion, this is the first extensive research on the correlation between PTPN family expression and immune characterization in BrCa. As results, PTPN7 expression is associated with immuno-hot tumors and could be a promising predictive biomarker for immunotherapy in not only BrCa but multiple cancers.

Keywords: PTPN; bioinformatics; biomarker; breast cancer; immune infiltration.