Abstract
PTPN6 (protein tyrosine phosphatase nonreceptor type 6), a tyrosine phosphatase, is known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. Previous studies have demonstrated that PTPN6 expression is relatively elevated in several malignancies. However, the role of PTPN6 in bladder cancer (BC) remains unclear. The purpose of this study was to explore the prognostic value of PTPN6 in BC. RNA-seq data from The Cancer Genome Atlas (TCGA) was used to identify the expression level of PTPN6 in BC. The relationship between clinical pathologic features and PTPN6 were analyzed with the Wilcoxon signed-rank test. The prognostic and predictive value of PTPN6 was evaluated by survival analysis and nomogram. Gene Set Enrichment Analysis (GSEA) was conducted to explore the potential molecular mechanisms of PTPN6 in BC. Finally, Tumor Immune Estimation Resource (TIMER) was applied to investigate the relationship between PTPN6 and immune cell infiltration in the tumor microenvironment. Results indicated that PTPN6 was overexpressed in BC tissues compared with normal bladder tissues and was significantly correlated with grade, stage, T, and N. Survival analysis showed that low expression of PTPN6 was significantly related to the poor overall survival (OS) in BC patients. Coexpression analysis showed that PTPN6 and TNFRSF14 (Tumor necrosis factor receptor superfamily member 14) have a close correlation in BC. GSEA showed that multiple cancer-associated signaling pathways are differentially enriched in the PTPN6 high expression phenotype. Moreover, the expression level of PTPN6 was positively associated with the infiltration of B cells, CD4+T cells, dendritic cells, and neutrophils and negatively associated with CD8+ T cells and macrophages in BC. In conclusion, we identified that PTPN6 may be a novel prognostic biomarker in BC based on the TCGA database. Further clinical trials are needed to confirm our observations and mechanisms underlying the prognostic value of PTPN6 in BC also deserve further experimental exploration.
Highlights
IntroductionSignificant progress has been made regarding the mechanisms, diagnosis, and therapy of Bladder cancer (BC) [2]
Bladder cancer (BC) is the most common malignant neoplasm in the urinary system [1]
No previous reports showed the prognostic value of PTPN6 in BC
Summary
Significant progress has been made regarding the mechanisms, diagnosis, and therapy of BC [2]. The high recurrence rate of nonmuscle invasive BC and the poor prognosis of advanced BC are still the main obstacles to the treatment of BC. The mechanism of BC research remains poorly understand, but genetic, epigenetics, and environmental factors are certainly involved in the tumorigenesis and progression of BC. Over the past few years, the advances in genomic methods have expanded our knowledge about gene expression, genetic, and epigenetic alterations at the pan-genomic level in various malignancies. Genomic studies led to the identification of tumor subgroups that have distinct biology and variable prognosis allowing for the development of prognostic molecular markers [3]. PTPN6 is a nonreceptor protein tyrosine phosphatase that can act as a tumor suppressor by dephosphorylating oncogenic
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