Xu Haoya, Zou Ruoyao, Liu Jiyu, Zhu Liancheng
Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning, China.
Key Laboratory of Maternal-Fetal Medicine of Liaoning Province and Key Laboratory of Obstetrics and Gynecology of Higher Education of Liaoning Province, Shenyang 110004, Liaoning, China.
J Oncol. 2021 Mar 6;2021:6653247. doi: 10.1155/2021/6653247. eCollection 2021.
To identify mRNA expression-based stemness index- (mRNAsi-) related genes and build an mRNAsi-related risk signature for endometrial cancer.
We collected mRNAsi data of endometrial cancer samples from The Cancer Genome Atlas (TCGA) and analyzed their relationship with the main clinicopathological characteristics and prognosis of endometrial cancer patients. We screened the top 50% of the genes in TCGA for weighted gene correlation network analysis (WGCNA) to explore mRNAsi-related gene sets. Among these mRNAsi-related genes, we further screened for those related to the prognosis of endometrial cancer patients via univariate Cox regression analysis and least absolute shrinkage and selection operator (LASSO) regression analysis. Using stepwise multivariate Cox regression analysis, a stemness index-related risk signature was constructed. Finally, we identified potential prognostic biomarkers for endometrial cancer by combining the GEO database and immunohistochemical staining.
The mRNAsi of endometrial cancer samples was significantly higher than that of normal samples and was related to the International Federation of Gynecology and Obstetrics (FIGO) stage, pathological grade, postoperative tumor status, and overall survival of endometrial cancer patients. We identified 21 mRNAsi-related gene modules, and 1,324 genes were obtained from the most relevant module. TCGA samples were divided into training and validation cohorts, and the training cohort was used to construct a nine-mRNAsi-related gene signature (, , , , , , , , and ). High-risk and low-risk patients had significant prognostic differences, and the risk signature could accurately predict their 1-, 3-, and 5-year survival. The nomogram composed of risk score and multiple clinicopathological features could accurately predict 1-, 3-, and 5-year survival. Finally, CD3EAP was found to be a novel prognostic biomarker for endometrial cancer.
Endometrial cancer cell stemness is related to patient prognosis. The nine-gene risk signature is an independent prognostic factor and can accurately predict endometrial cancer patient prognosis.
鉴定基于mRNA表达的干性指数(mRNAsi)相关基因,并构建子宫内膜癌的mRNAsi相关风险特征。
我们从癌症基因组图谱(TCGA)收集了子宫内膜癌样本的mRNAsi数据,并分析了它们与子宫内膜癌患者主要临床病理特征和预后的关系。我们筛选了TCGA中前50%的基因进行加权基因共表达网络分析(WGCNA),以探索mRNAsi相关基因集。在这些mRNAsi相关基因中,我们通过单变量Cox回归分析和最小绝对收缩和选择算子(LASSO)回归分析进一步筛选出与子宫内膜癌患者预后相关的基因。使用逐步多变量Cox回归分析,构建了一个干性指数相关风险特征。最后,我们通过结合GEO数据库和免疫组织化学染色鉴定了子宫内膜癌的潜在预后生物标志物。
子宫内膜癌样本的mRNAsi显著高于正常样本,且与国际妇产科联盟(FIGO)分期、病理分级、术后肿瘤状态及子宫内膜癌患者的总生存期相关。我们鉴定了21个mRNAsi相关基因模块,并从最相关的模块中获得了1324个基因。将TCGA样本分为训练组和验证组,训练组用于构建一个九基因的mRNAsi相关基因特征(、、、、、、、和)。高风险和低风险患者具有显著的预后差异,且该风险特征可准确预测其1年、3年和5年生存率。由风险评分和多个临床病理特征组成的列线图可准确预测1年、3年和5年生存率。最后,发现CD3EAP是子宫内膜癌的一种新型预后生物标志物。
子宫内膜癌细胞干性与患者预后相关。九基因风险特征是一个独立的预后因素,可准确预测子宫内膜癌患者的预后。