Lan Tianfeng, Wang Yachao, Miao Jinxin, Guo Haoran, Wang Zheng, Wang Jianyao, Zhang Chunyang, Yang Panpan, Zhang Zhongxian, Dunmall Louisa Chard, Wang Yaohe
State Key Laboratory of Esophageal Cancer Prevention and Treatment, Sino-British Research Center for Molecular Oncology, National Center for the International Research in Cell and Gene Therapy, School of Basic Sciences, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, China.
Academy of Chinese Medicine Science, Henan University of Chinese Medicine, Zhengzhou, China.
Front Mol Biosci. 2022 Jul 12;9:887059. doi: 10.3389/fmolb.2022.887059. eCollection 2022.
Deoxythymidylate kinase (DTYMK) serves as a pyrimidine metabolic rate-limiting enzyme that catalyzes deoxythymidine monophosphate (dTMP) to generate deoxythymidine diphosphate (dTDP). It remains unclear whether DTYMK expression has the potential to predict outcome and immune cell infiltration in cancers. DTYMK expression profile was analyzed using Oncomine, TIMER, GEPIA and UALCAN databases. The influence of DTYMK on immune infiltration was examined using TIMER and TISIDB databases. DTYMK interactive gene hub and co-expressing genes were obtained and analyzed by STRING and Linkedomics, respectively. The relationship between DTYMK expression and patient prognosis was validated using GEPIA, Kaplan-Meier plotter, and PrognoScan databases. The functions of DTYMK in cancer cells were also biologically validated . DTYMK expression was elevated in tumor tissues compared with their control counterparts. DTYMK expression varied in different stages and discriminatorily distributed in different immune and molecular subtypes. Higher expression of DTYMK predicted worse outcome in several cancer types such as liver hepatocellular carcinoma (LIHC) and lung adenocarcinoma (LUAD). High DTYMK expression was positively or negatively correlated with immune cell infiltration, including B cell, CD8 cell, CD4 T cell, macrophage, neutrophil and dendritic cell, depending on the type of cancers. Additionally, DTYMK co-expressing genes participated in pyrimidine metabolism as well as in T helper cell differentiation in LIHC and LUAD. , knockdown of DTYMK suppressed cell migration of liver and lung cancer cells. DTYMK might be taken as an useful prognostic and immunological marker in cancers and further investigation is warrented.
脱氧胸苷酸激酶（DTYMK）是一种嘧啶代谢限速酶，催化一磷酸脱氧胸苷（dTMP）生成二磷酸脱氧胸苷（dTDP）。DTYMK表达是否具有预测癌症预后和免疫细胞浸润的潜力仍不清楚。使用Oncomine、TIMER、GEPIA和UALCAN数据库分析DTYMK表达谱。使用TIMER和TISIDB数据库研究DTYMK对免疫浸润的影响。分别通过STRING和Linkedomics获得并分析DTYMK相互作用基因枢纽和共表达基因。使用GEPIA、Kaplan-Meier plotter和PrognoScan数据库验证DTYMK表达与患者预后之间的关系。DTYMK在癌细胞中的功能也得到了生物学验证。与对照组织相比，肿瘤组织中DTYMK表达升高。DTYMK表达在不同阶段有所不同，并且在不同的免疫和分子亚型中存在差异分布。DTYMK高表达在几种癌症类型中，如肝细胞肝癌（LIHC）和肺腺癌（LUAD），预示着更差的预后。根据癌症类型，DTYMK高表达与免疫细胞浸润呈正相关或负相关，包括B细胞、CD8细胞、CD4 T细胞、巨噬细胞、中性粒细胞和树突状细胞。此外，在LIHC和LUAD中，DTYMK共表达基因参与嘧啶代谢以及辅助性T细胞分化。敲低DTYMK可抑制肝癌和肺癌细胞的迁移。DTYMK可能是一种有用的癌症预后和免疫标志物，值得进一步研究。
