Xie Hui, Guo Linpei, Wang Zhun, Peng Shuanghe, Ma Qianwang, Yang Zhao, Shang Zhiqun, Niu Yuanjie
Department of Urology, Tianjin Institute of Urology, the Second Hospital of Tianjin Medical University, Tianjin, China.
Department of Urology, the Affiliated Wuxi No. 2 People's Hospital of Nanjing Medical University, Wuxi, China.
Front Genet. 2022 Apr 26;13:778850. doi: 10.3389/fgene.2022.778850. eCollection 2022.
It has been reported that thymidine kinase 1 (TK1) was up-regulated in multiple malignancies and participated in the regulation of tumor malignant behavior. However, its specific role in prostate cancer (PCa) remains unclear. TK1 expression in PCa patients and cell lines was identified via crossover analysis of the public datasets. A series of experiments and models was applied to investigate the function of TK1 in PCa. Functional enrichment analyses were further conducted to explore the underlying mechanism. Additionally, TISIDB was applied to explore the correlation between TK1 expression and tumor-infiltrating lymphocytes, immune subtypes, and immune regulatory factors. TK1 expression was significantly up-regulated in PCa patients and cell lines. TK1 ablation inhibited tumor cell proliferation and migration potential, and experiments showed that TK1 inactivation can significantly restrain tumor growth. Functional enrichment analysis revealed TK1-related hub genes (AURKB, CCNB2, CDC20, CDCA5, CDK1, CENPA, CENPM, KIF2C, NDC80, NUF2, PLK1, SKA1, SPC25, ZWINT), and found that TK1 was closely involved in the regulation of cell cycle. Moreover, elevated mRNA expression of TK1 was related with higher Gleason score, higher clinical stage, higher pathological stage, higher lymph node stage, shorter overall survival, and DFS in PCa patients. Particularly, TK1 represented attenuated expression in C3 PCa and was related with infiltration of CD4, CD8 T cells, and dendritic cells as well as immunomodulator expression. Our study indicates that TK1 is a prognostic predictor correlated with poor outcomes of PCa patients, and for the first time represented that TK1 can promote the progression of PCa. Therefore, TK1 may be a potential diagnostic and prognostic biomarker, as well as a therapeutic target for PCa.
据报道,胸苷激酶1(TK1)在多种恶性肿瘤中上调,并参与肿瘤恶性行为的调控。然而,其在前列腺癌(PCa)中的具体作用仍不清楚。通过对公共数据集的交叉分析确定了PCa患者和细胞系中TK1的表达。应用一系列实验和模型来研究TK1在PCa中的功能。进一步进行功能富集分析以探索潜在机制。此外,应用TISIDB来探索TK1表达与肿瘤浸润淋巴细胞、免疫亚型和免疫调节因子之间的相关性。TK1表达在PCa患者和细胞系中显著上调。TK1缺失抑制肿瘤细胞增殖和迁移潜能,实验表明TK1失活可显著抑制肿瘤生长。功能富集分析揭示了与TK1相关的枢纽基因(AURKB、CCNB2、CDC20、CDCA5、CDK1、CENPA、CENPM、KIF2C、NDC80、NUF2、PLK1、SKA1、SPC25、ZWINT),并发现TK1密切参与细胞周期调控。此外,PCa患者中TK1 mRNA表达升高与更高的Gleason评分、更高的临床分期、更高的病理分期、更高的淋巴结分期、更短的总生存期和无病生存期相关。特别是,TK1在C3 PCa中表达减弱,并且与CD4、CD8 T细胞和树突状细胞的浸润以及免疫调节剂表达相关。我们的研究表明,TK1是与PCa患者不良预后相关的预后预测指标,并且首次表明TK1可促进PCa的进展。因此,TK1可能是一种潜在诊断和预后生物标志物,以及PCa的治疗靶点。