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胸苷激酶1(TK1)的甲基化状态与前列腺癌中的免疫浸润相关。

Methylation status of TK1 correlated with immune infiltrates in prostate cancer.

作者信息

Zhang Chenming, Ma Sicheng, Hao Xiaohui, Wang Zulong, Sun Zixue

机构信息

The Second Clinical Medical School, Henan University of Chinese Medicine, Zhengzhou, China.

Andrology Department, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, China.

出版信息

Front Genet. 2022 Aug 11;13:899384. doi: 10.3389/fgene.2022.899384. eCollection 2022.

Abstract

TK1 is overexpressed in numerous cancers and is associated with to a poor prognosis. However, the relationship between methylation status of TK1 and Immune Infiltrates in Prostate Cancer (PCa) is unknown. The goal of this study was to use comprehensive bioinformatic analyses to elucidate the involvement relationship between methylation status of TK1 and Immune Infiltrates in PCa. TK1 mRNA expression and methylation data in PCa were investigated via GEPIA, TIMER, and UALCAN coupled with MEXPRESS data resources. We employed the LinkedOmics data resource to determine the signaling cascades linked to TK1 expression. Single-cell analysis was performed using the CancerSEA data resource. GeneMANIA and CancerSEA were used to analyze the correlation between TK1 and TK1 coexpressed genes. In addition, TIMER and TISIDB were adopted to assess tumor-invading immune cells and immunomodulators. CTD was utilized to detect the drugs acting on TK1. This study found that TK1 was overexpressed in PCa, and its contents were linked to tumor stage and prognosis. Genes co-expressed with TK1 were enriched in cascades involved in the ribosome, cell cycle, oxidative phosphorylation, DNA replication, oocyte meiosis, and the proteasome. The expression of TK1 along with its methylation status was found to be linked to tumor-invading immune cells, as well as PCa immunomodulators. We also examined the prospect of employing TK1 as a possible target for PCa therapy. This work provides the clinical value of TK1 hypermethylation in PCa and highlights new insights into its novel immunomodulatory functions.

摘要

胸苷激酶1(TK1)在多种癌症中过表达,且与预后不良相关。然而,TK1甲基化状态与前列腺癌(PCa)免疫浸润之间的关系尚不清楚。本研究的目的是通过全面的生物信息学分析来阐明PCa中TK1甲基化状态与免疫浸润之间的关联关系。通过GEPIA、TIMER和UALCAN结合MEXPRESS数据资源,研究了PCa中TK1 mRNA表达和甲基化数据。我们利用LinkedOmics数据资源来确定与TK1表达相关的信号级联。使用CancerSEA数据资源进行单细胞分析。利用GeneMANIA和CancerSEA分析TK1与其共表达基因之间的相关性。此外,采用TIMER和TISIDB评估肿瘤浸润免疫细胞和免疫调节剂。利用CTD检测作用于TK1的药物。本研究发现,TK1在PCa中过表达,其含量与肿瘤分期和预后相关。与TK1共表达的基因富集于核糖体、细胞周期、氧化磷酸化、DNA复制、卵母细胞减数分裂和蛋白酶体相关的级联反应中。发现TK1的表达及其甲基化状态与肿瘤浸润免疫细胞以及PCa免疫调节剂有关。我们还研究了将TK1用作PCa治疗潜在靶点的前景。这项工作提供了TK1高甲基化在PCa中的临床价值,并突出了对其新型免疫调节功能的新见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6108/9403003/7818b563e068/fgene-13-899384-g001.jpg

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