GTSE1 is well correlated with tumor progression; however, little is known regarding its role in liver cancer prognosis. By analyzing the hepatocellular carcinoma (HCC) datasets in GEO and TCGA databases, we showed that high expression of GTSE1 was correlated with advanced pathologic stage and poor prognosis of HCC patients. To investigate underlying molecular mechanism, we generated GTSE1 knockdown HCC cell line and explored the effects of GTSE1 deficiency in cell growth. Between GTSE1 knockdown and wild-type HCC cells, we identified 979 differentially expressed genes (520 downregulated and 459 upregulated genes) in the analysis of microarray-based gene expression profiling. Functional enrichment analysis of DEGs suggested that S phase was dysregulated without GTSE1 expression, which was further verified from flow cytometry analysis. Moreover, three other DEGs: CDC20, PCNA, and MCM6, were also found contributing to GTSE1-related cell cycle arrest and to be associated with poor overall survival of HCC patients. In conclusion, GTSE1, together with CDC20, PCNA, and MCM6, may synergistically promote adverse prognosis in HCC by activating cell cycle. Genes like GTSE1, CDC20, PCNA, and MCM6 may be promising prognostic molecular biomarkers in liver cancer.

中文翻译：

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GTSE1，CDC20，PCNA和MCM6协同影响细胞周期中的调节并指示肝癌的不良预后。

GTSE1与肿瘤进展密切相关；然而，关于其在肝癌预后中的作用知之甚少。通过分析GEO和TCGA数据库中的肝细胞癌（HCC）数据集，我们发现GTSE1的高表达与HCC患者的病理晚期和预后不良相关。为了研究潜在的分子机制，我们生成了GTSE1敲低的HCC细胞系，并探讨了GTSE1缺乏对细胞生长的影响。在GTSE1基因敲低和野生型HCC细胞之间，我们在基于微阵列的基因表达谱分析中鉴定了979个差异表达的基因（520个下调的基因和459个上调的基因）。DEG的功能富集分析表明，没有GTSE1表达的S期失调，这已从流式细胞仪分析中得到进一步证实。此外，还发现了其他三个DEG：CDC20，PCNA和MCM6，它们与GTSE1相关的细胞周期停滞有关，并且与HCC患者的总体生存期较差有关。总之，GTSE1与CDC20，PCNA和MCM6可能通过激活细胞周期协同促进肝癌的不良预后。GTSE1，CDC20，PCNA和MCM6等基因可能是肝癌有希望的预后分子生物标志物。