Introduction: Hepatocellular carcinoma (HCC) is the most common malignant tumor of the liver. Identifying specific molecular markers that can predict HCC prognosis is extremely important. The protein deoxythymidylate kinase (DTYMK) has been reported to contribute to unfavorable prognosis in non-small cell lung cancer patients, but its role in the prediction of HCC patient prognosis has not been clarified.
Methods: Samples from the TCGA and GEO databases were consecutively enrolled for gene expression analysis, clinicopathology analysis, immune microenvironment analysis and chemotherapeutic response prediction. The results were validated using 86 samples from the First Affiliated Hospital of Sun Yat-sen University. Cox regression analysis was used to analyze the effect of DTYMK on progression-free survival (PFS) and overall survival (OS). Functional enrichment analysis was used to describe the marker pathways that were significantly related to DTYMK. TIMER (Tumor Immune Estimation Resource), TISIDB (Tumor and Immune System Interaction DataBase) and CIBERSORT (Cell type Identification By Estimating Relative Subsets Of RNA Transcripts) were used to explore the immune microenvironment.
Results: We found that DTYMK expression upregulation is associated with poor prognosis in HCC patients and tightly related to the pathways regulating the cell cycle and acid metabolism. Our findings revealed that hepatocellular carcinoma cell lines with high DTYMK expression were more sensitive to sorafenib and many other chemotherapeutic drugs. We also found an inhibiting effect of DTYMK on the immune microenvironment in the process of tumorigenesis.
Discussion: We found that DTYMK has potential as a new prognostic and chemotherapeutic response biomarker for HCC patients and correlates with the immune microenvironment in HCC. However, there are some deficiencies in our study. First, this is a retrospective study that may lead to selection bias. Second, the protein expression of DTYMK was investigated via immunohistochemical analysis. Finally, we did not explore the exact underlying molecular mechanisms of DTYMK in tumorigenesis in this study, which is needed to be clarified in future research.

Keywords: hepatocellular carcinoma, DTYMK, cell cycle, immune infiltration, TCGA


中文翻译：

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DTYMK 表达预测肝细胞癌的预后和化疗反应并与免疫浸润相关

简介：肝细胞癌（HCC）是肝脏最常见的恶性肿瘤。识别可以预测 HCC 预后的特定分子标志物极为重要。据报道，蛋白质脱氧胸苷酸激酶 (DTYMK) 导致非小细胞肺癌患者预后不良，但其在预测 HCC 患者预后中的作用尚未阐明。
方法：来自 TCGA 和 GEO 数据库的样本被连续纳入基因表达分析、临床病理学分析、免疫微环境分析和化疗反应预测。使用来自中山大学第一附属医院的 86 个样本对结果进行了验证。Cox回归分析用于分析DTYMK对无进展生存期（PFS）和总生存期（OS）的影响。功能富集分析用于描述与 DTYMK 显着相关的标记途径。TIMER (Tumor Immune Estimation Resource)、TISIDB (Tumor and Immune System Interaction Database) 和 CIBERSORT (Cell type Identification By Estimating Relative Subsets of RNA Transcripts) 用于探索免疫微环境。
结果：我们发现 DTYMK 表达上调与 HCC 患者的不良预后相关，并且与调节细胞周期和酸代谢的途径密切相关。我们的研究结果表明，具有高 DTYMK 表达的肝细胞癌细胞系对索拉非尼和许多其他化疗药物更敏感。我们还发现 DTYMK 在肿瘤发生过程中对免疫微环境有抑制作用。
讨论：我们发现 DTYMK 具有作为 HCC 患者新的预后和化疗反应生物标志物的潜力，并且与 HCC 中的免疫微环境相关。但是，我们的研究也存在一些不足。首先，这是一项可能导致选择偏倚的回顾性研究。其次，通过免疫组织化学分析研究了 DTYMK 的蛋白质表达。最后，我们没有在本研究中探索 DTYMK 在肿瘤发生中的确切潜在分子机制，这需要在未来的研究中加以阐明。

关键词：肝细胞癌，DTYMK，细胞周期，免疫浸润，TCGA