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.

中文翻译：

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膀胱癌中PTPN6的分析：基于TCGA的探索性研究。

PTPN6（蛋白酪氨酸磷酸酶非受体6型），酪氨酸磷酸酶，是一种信号分子，可调节多种细胞过程，包括细胞生长，分化，有丝分裂周期和致癌转化。先前的研究表明，PTPN6表达在某些恶性肿瘤中相对升高。但是，PTPN6在膀胱癌（BC）中的作用尚不清楚。这项研究的目的是探讨PTPN6在BC中的预后价值。来自癌症基因组图谱（TCGA）的RNA-seq数据用于鉴定BC中PTPN6的表达水平。临床病理特征与PTPN6的关系用Wilcoxon符号秩检验进行了分析。通过生存分析和列线图评估PTPN6的预后和预测价值。进行了基因集富集分析（GSEA），以探讨PTPN6在卑诗省的潜在分子机制。最后，应用肿瘤免疫估计资源（TIMER）来研究肿瘤微环境中PTPN6与免疫细胞浸润的关系。结果表明，与正常膀胱组织相比，PTPN6在BC组织中过表达，并且与等级，分期，T和N显着相关。生存分析表明PTPN6的低表达与BC患者总体生存率（OS）差有关。共表达分析表明，PTPN6和TNFRSF14（肿瘤坏死因子受体超家族成员14）与BC密切相关。GSEA显示PTPN6高表达表型差异性地富集了多种与癌症相关的信号通路。此外，PTPN6的表达水平与B细胞，CD4 + T细胞，树突状细胞和嗜中性粒细胞的浸润呈正相关，与BC中CD8 + T细胞和巨噬细胞呈负相关。总之，我们确定了PTPN6可能是基于TCGA数据库的BC省新的预后生物标志物。需要进一步的临床试验来确认我们的观察结果，PTPN6在卑诗省预后价值的潜在机制也值得进一步的实验探索。