Deoxythymidylate Kinase as a Promising Marker for Predicting Prognosis and Immune Cell Infiltration of Pan-cancer.
Deoxythymidylate Kinase as a Promising Marker for Predicting Prognosis and Immune Cell Infiltration of Pan-cancer.
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DOI：
10.3389/fmolb.2022.887059
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发表时间：
2022
影响因子：
5
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背景：脱氧胸苷酸激酶（DTYMK）作为嘧啶代谢限速酶，催化脱氧胸苷单磷酸（dTMP）生成脱氧胸苷二磷酸（dTDP）。目前尚不清楚 DTYMK 表达是否具有预测癌症结果和免疫细胞浸润的潜力。 方法：使用 Oncomine、TIMER、GEPIA 和 UALCAN 数据库分析 DTYMK 表达谱。使用 TIMER 和 TISIDB 数据库检查了 DTYMK 对免疫浸润的影响。 DTYMK交互基因中心和共表达基因分别通过STRING和Linkedomics获得和分析。使用 GEPIA、Kaplan-Meier 绘图仪和 PrognoScan 数据库验证了 DTYMK 表达与患者预后之间的关系。 DTYMK 在癌细胞中的功能也在体外得到了生物学验证。 结果：与对照组织相比，肿瘤组织中 DTYMK 表达升高。 DTYMK 表达在不同阶段存在差异，并且在不同的免疫和分子亚型中分布有区别。 DTYMK 的较高表达预示着多种癌症类型的预后较差，例如肝细胞癌 (LIHC) 和肺腺癌 (LUAD)。 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，具体取决于癌症类型。此外，DTYMK 共表达基因参与嘧啶代谢以及 LIHC 和 LUAD 中 T 辅助细胞分化。在体外，DTYMK 的敲低抑制了肝癌和肺癌细胞的细胞迁移。 结论：DTYMK 可能被视为癌症的有用预后和免疫学标志物，需要进一步研究。
Background: 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. Methods: 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 in vitro. Results: 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. In vitro, knockdown of DTYMK suppressed cell migration of liver and lung cancer cells. Conclusion: DTYMK might be taken as an useful prognostic and immunological marker in cancers and further investigation is warrented.