BACKGROUND The morbidity and mortality of endometrial tumors, a common type of malignant cancer in women, have increased in recent years. POLE encodes the DNA polymerase ε, which is responsible for the leading strand DNA replication. Somatic mutations of POLE have been acknowledged in numerous cancers, resulting in the accumulation of DNA errors, leading to ultra-mutated tumors. Mutations in the exonuclease domain of POLE have been reported to improve progression-free survival in endometrial cancer. However, the potential relationship and underlying mechanism between POLE mutations and the prognosis of endometrial cancer patients remains unclear. METHODS The whole exome sequencing data, RNA sequencing data, and clinical information were obtained from the TCGA database and employed for the analyses in this study. The detailed mutational information was analyzed using whole exome sequencing data and the mutated genes were shown with OncoPlot. The survival curves and cox proportional hazards regression analysis were used to accessed patient prognosis, the association of clinical characteristics and prognosis. Differentially expressed genes were analyzed by the edgeR R/Bioconductor package, then the GSEA Pre-ranked tool was used for Gene Set Enrichment Analysis (GSEA) to estimate the function of genes. Expression values were clustered using hierarchical clustering with Euclidean distance and ward linkage by the dendextend R package. RESULTS POLE mutational status was proven to be an independent prognostic factor for endometrial cancer patients. Patients with somatic POLE mutations presented a favorable prognosis. POLE mutations regulated glycolysis and cytokine secretion, affecting cell metabolism and immune response. Autocrine motility factor (AMF)/PGI and AMFR/gp78 exhibited higher expression levels in POLE mutant patients. The comprehensive high expressions of AMFR/gp78 and low expression of POLE were associated with the favorable prognosis of endometrial cancer patients. CONCLUSIONS This study showed the POLE mutations a vital factor in endometrial cancer patients, leading to a higher expression of AMF/PGI and AMFR/gp78. These results suggested comprehensive consideration of the POLE mutations, expression of AMF/PGI and AMFR/gp78 may provide a more feasible and effective approach for the treatment of endometrial cancer, which might improve the prognosis.

中文翻译：

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POLE突变可通过AMF / AMFR信号转导调节细胞代谢，从而改善子宫内膜癌的预后。

背景技术近年来，子宫内膜肿瘤的发病率和死亡率增加，子宫内膜肿瘤是女性的恶性癌症的一种常见类型。POLE编码DNA聚合酶ε，负责前导链DNA复制。POLE的体细胞突变已在许多癌症中得到公认，导致DNA错误的积累，从而导致了超突变的肿瘤。据报道，POLE的核酸外切酶结构域突变可改善子宫内膜癌的无进展生存期。然而，POLE突变与子宫内膜癌患者预后之间的潜在关系和潜在机制尚不清楚。方法完整的外显子组测序数据，RNA测序数据和临床信息均来自TCGA数据库，并用于本研究的分析。使用完整的外显子组测序数据分析详细的突变信息，并使用OncoPlot显示突变的基因。使用生存曲线和Cox比例风险回归分析分析患者的预后，临床特征与预后之间的关系。通过edgeR R / Bioconductor软件包分析差异表达的基因，然后使用GSEA预排名工具进行基因集富集分析（GSEA）来评估基因的功能。通过使用dendextend R包使用欧几里德距离和病房链接的层次聚类对表达值进行聚类。结果证明POLE突变状态是子宫内膜癌患者的独立预后因素。体细胞POLE突变的患者预后良好。POLE突变调节糖酵解和细胞因子分泌，影响细胞代谢和免疫反应。自分泌运动因子（AMF）/ PGI和AMFR / gp78在POLE突变患者中表现出较高的表达水平。AMFR / gp78的高表达和POLE的低表达与子宫内膜癌患者的良好预后有关。结论这项研究表明POLE突变是子宫内膜癌患者的重要因素，导致AMF / PGI和AMFR / gp78的高表达。这些结果提示对POLE突变的全面考虑，AMF / PGI和AMFR / gp78的表达可能为子宫内膜癌的治疗提供了一种更可行，更有效的方法，可能会改善预后。自分泌运动因子（AMF）/ PGI和AMFR / gp78在POLE突变患者中表现出较高的表达水平。AMFR / gp78的高表达和POLE的低表达与子宫内膜癌患者的良好预后有关。结论这项研究表明POLE突变是子宫内膜癌患者的重要因素，导致AMF / PGI和AMFR / gp78的高表达。这些结果提示对POLE突变的全面考虑，AMF / PGI和AMFR / gp78的表达可能为子宫内膜癌的治疗提供了一种更可行，更有效的方法，可能会改善预后。自分泌运动因子（AMF）/ PGI和AMFR / gp78在POLE突变患者中表现出较高的表达水平。AMFR / gp78的高表达和POLE的低表达与子宫内膜癌患者的良好预后有关。结论这项研究表明POLE突变是子宫内膜癌患者的重要因素，导致AMF / PGI和AMFR / gp78的高表达。这些结果提示对POLE突变的全面考虑，AMF / PGI和AMFR / gp78的表达可能为子宫内膜癌的治疗提供了一种更可行，更有效的方法，可能会改善预后。AMFR / gp78的高表达和POLE的低表达与子宫内膜癌患者的良好预后相关。结论这项研究表明POLE突变是子宫内膜癌患者的重要因素，导致AMF / PGI和AMFR / gp78的高表达。这些结果提示对POLE突变的全面考虑，AMF / PGI和AMFR / gp78的表达可能为子宫内膜癌的治疗提供了一种更可行，更有效的方法，可能会改善预后。AMFR / gp78的高表达和POLE的低表达与子宫内膜癌患者的良好预后有关。结论这项研究表明POLE突变是子宫内膜癌患者的重要因素，导致AMF / PGI和AMFR / gp78的高表达。这些结果提示对POLE突变的全面考虑，AMF / PGI和AMFR / gp78的表达可能为子宫内膜癌的治疗提供了一种更可行，更有效的方法，可能会改善预后。