Department of Endocrinology, The First Affiliated Hospital of Yangtze University, Jingzhou First People's Hospital, Jingzhou, Hubei, China.
Department of Hubei Provincial Clinical Research Center for Personalized Diagnosis and Treatment of Cancer, The First Affiliated Hospital of Yangtze University, Jingzhou First People's Hospital, Jingzhou, Hubei, China.
Front Immunol. 2024 Oct 16;15:1464421. doi: 10.3389/fimmu.2024.1464421. eCollection 2024.
Diabetes is associated with the incidence and prognosis of various malignancies, most notably endometrial cancer (EC). This study investigated the connection between diabetes and EC, with a specific focus on elucidating the biological implications of the diabetes mellitus (DM)-related gene WFS1.
Using the CTD, GeneCards, and GSEA databases, we identified WFS1 as a diabetes-related gene and then conducted an extensive investigation focusing on WFS1 in the context of EC. First, we identified WFS1 as the target gene and obtained EC data from the TCGA database. Then, comprehensive analyses and verification experiments, including differential expression analysis, prognostic modeling, functional enrichment analysis, gene mutation profiling, assessment of immune cell infiltration, immunophenoscore (IPS), tumor stemness index scoring, drug sensitivity analysis, single-cell transcriptomic analysis, glycolytic pathway analysis, and clinical verification, were performed to comprehensively evaluate the clinical value of WFS1 in EC.
The EC group had significantly lower WFS1 expression, with an AUC of 0.857 for the ROC diagnostic curve. Overall survival analysis revealed that WFS1 was an independent risk factor for EC; low WFS1 expression was correlated with a poor prognosis. Stemness index analysis revealed that decreased WFS1 expression was associated with increased tumor grade and enhanced tumor stemness, suggesting increased malignancy of EC. In addition, WFS1 expression was correlated with tumor microenvironment features such as immune cell infiltration. WFS1 was also associated with tumor drug resistance.
EC patients with low WFS1 expression have a worse prognosis. WFS1 can be used as diagnostic and prognostic marker for EC.
糖尿病与多种恶性肿瘤的发生和预后相关，尤其是子宫内膜癌（EC）。本研究探讨了糖尿病与 EC 之间的关系，特别关注阐明与糖尿病相关的 WFS1 基因的生物学意义。
我们使用 CTD、GeneCards 和 GSEA 数据库，鉴定出 WFS1 是一个与糖尿病相关的基因，并对其在 EC 中的作用进行了广泛的研究。首先，我们确定 WFS1 是靶基因，并从 TCGA 数据库中获得 EC 数据。然后，进行了全面的分析和验证实验，包括差异表达分析、预后建模、功能富集分析、基因突变分析、免疫细胞浸润评估、免疫表型评分（IPS）、肿瘤干性指数评分、药物敏感性分析、单细胞转录组分析、糖酵解通路分析和临床验证，以全面评估 WFS1 在 EC 中的临床价值。
EC 组的 WFS1 表达明显降低，ROC 诊断曲线的 AUC 为 0.857。总体生存分析显示，WFS1 是 EC 的独立危险因素；低 WFS1 表达与不良预后相关。干性指数分析显示，WFS1 表达降低与肿瘤分级增加和肿瘤干性增强相关，提示 EC 的恶性程度增加。此外，WFS1 表达与肿瘤微环境特征如免疫细胞浸润有关。WFS1 还与肿瘤药物耐药性有关。
EC 患者中 WFS1 低表达者预后较差。WFS1 可作为 EC 的诊断和预后标志物。
