Liu Lili, Zhu Hongcang, Wang Pei, Wu Suzhen
TCM Gynecology Department, Foshan Fosun Chancheng Hospital, Foshan Clinical Medical School of Guangzhou University of Chinese Medicine, Foshan, China.
Foshan Retirement Center for Retired Cadres, Guangdong Military Region of the PLA, Foshan, China.
Front Genet. 2022 Jun 13;13:923263. doi: 10.3389/fgene.2022.923263. eCollection 2022.
The prognosis of cervical cancer (CC) is poor and not accurately reflected by the primary tumor node metastasis staging system. Our study aimed to develop a novel survival-prediction model. Hallmarks of CC were quantified using single-sample gene set enrichment analysis and univariate Cox proportional hazards analysis. We linked gene expression, hypoxia, and angiogenesis using weighted gene co-expression network analysis (WGCNA). Univariate and multivariate Cox regression was combined with the random forest algorithm to construct a prognostic model. We further evaluated the survival predictive power of the gene signature using Kaplan-Meier analysis and receiver operating characteristic (ROC) curves. Hypoxia and angiogenesis were the leading risk factors contributing to poor overall survival (OS) of patients with CC. We identified 109 candidate genes using WGCNA and univariate Cox regression. Our established prognostic model contained six genes ( and ). Kaplan-Meier analysis indicated that high-risk patients had worse OS (hazard ratio = 4.63, < 0.001). Our model had high predictive power according to the ROC curve. The C-index indicated that the risk score was a better predictor of survival than other clinicopathological variables. Additionally, univariate and multivariate Cox regressions indicated that the risk score was the only independent risk factor for poor OS. The risk score was also an independent predictor in the validation set (GSE52903). Bivariate survival prediction suggested that patients exhibited poor prognosis if they had high z-scores for hypoxia or angiogenesis and high risk scores. We established a six-gene survival prediction model associated with hypoxia and angiogenesis. This novel model accurately predicts survival and also provides potential therapeutic targets.
宫颈癌(CC)的预后较差,且原发肿瘤淋巴结转移分期系统无法准确反映其预后情况。我们的研究旨在开发一种新型生存预测模型。使用单样本基因集富集分析和单变量Cox比例风险分析对CC的特征进行量化。我们通过加权基因共表达网络分析(WGCNA)将基因表达、缺氧和血管生成联系起来。将单变量和多变量Cox回归与随机森林算法相结合来构建预后模型。我们使用Kaplan-Meier分析和受试者工作特征(ROC)曲线进一步评估基因特征的生存预测能力。缺氧和血管生成是导致CC患者总生存期(OS)较差的主要危险因素。我们通过WGCNA和单变量Cox回归鉴定出109个候选基因。我们建立的预后模型包含6个基因(和)。Kaplan-Meier分析表明,高危患者的OS较差(风险比=4.63,<0.001)。根据ROC曲线,我们的模型具有较高的预测能力。C指数表明,风险评分比其他临床病理变量更能预测生存情况。此外,单变量和多变量Cox回归表明,风险评分是OS较差的唯一独立危险因素。在验证集(GSE52903)中,风险评分也是一个独立的预测指标。双变量生存预测表明,如果患者缺氧或血管生成的z评分较高且风险评分较高,则其预后较差。我们建立了一个与缺氧和血管生成相关的六基因生存预测模型。这个新型模型能够准确预测生存情况,还提供了潜在的治疗靶点。