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中国癌症防治杂志 ›› 2021, Vol. 13 ›› Issue (5): 511-517.doi: 10.3969/j.issn.1674-5671.2021.05.11

• 临床研究 • 上一篇    下一篇

卵巢癌免疫相关预后模型的构建与验证

  

  1. 中国人民解放军陆军军医大学第二附属医院妇科;中国人民解放军陆军军医大学毒理学研究所
  • 出版日期:2021-10-25 发布日期:2021-11-17
  • 通讯作者: 董训虎 E-mail:245437535@qq.com

Construction and validation of a novel immune-related prognostic signature of ovarian cancer

  • Online:2021-10-25 Published:2021-11-17

摘要: 目的 构建卵巢癌免疫相关预后模型并初步筛选预后标志物。方法 将癌症基因组图谱(TCGA)中卵巢癌样本按照7∶3的比例随机分为训练集和测试集,GSE26712作为外部验证集。通过limma软件包分析免疫相关的差异基因(IRDEGs),单因素Cox回归筛选预后相关的IRDEGs,通过LASSO回归和多因素Cox回归构建模型,采用受试者工作特征(ROC)曲线和C-index对模型进行评价。构建列线图模型,通过校准曲线和决策曲线评价列线图的预测性能。 结果 本研究在训练集中成功构建了包含11个基因(C5AR1、CX3CR1、CXCL11、CXCL13、IGF1、IL27RA、NFKBIB、PENK、PI3、PSMC1和PSME3)的预后模型,C-index为0.69,1、3、5年的曲线下面积分别为0.67、0.71和0.75;多因素Cox回归分析显示该风险模型是卵巢癌患者的独立预后因素(HR=2.58, 95%CI=2.15~3.25)。基于风险得分成功构建了列线图模型,其校准曲线拟合良好,决策曲线显示列线图在指导临床决策方面具有积极的净收益。结论 本研究构建的免疫相关预后模型在卵巢癌预后预测中具有良好的效能,其中的相关基因可能是卵巢癌患者免疫治疗的潜在标志物。

关键词: 卵巢癌, 生物信息学, 预后模型, 生物标志物, 癌症基因组图谱

Abstract: Objective To construct a novel immune-related prognostic model of ovarian cancer and to preliminarily screen the prognostic biomarkers. Methods The ovarian cancer samples from the TCGA database were randomly divided into a training cohort and a testing cohort according to the ratio of 7∶3, with GSE26712 being external validate cohort. The immune-related differential expressed genes (IRDEGs) were analyzed by “limma” package and the prognostic IRDEGs were screened by univariable Cox regression. The signatures were constructed by robust LASSO and multivariable Cox regression. Additionally, the receiver operating characteristic (ROC) curves and C-index were employed to evaluate the signatures. A nomogram was established, and the prediction performance of the nomogram was evaluated by calibration curves and decision curves. Results The 11-gene signature (C5AR1, CX3CR1, CXCL11, CXCL13, IGF1, IL27RA, NFKBIB, PENK, PI3, PSMC1 and PSME3) was successfully constructed in the training cohort with C-index of 0.69, the area under curves (AUC) at 1-, 3- and 5-year were 0.67, 0.71 and 0.75, respectively. Multivariable Cox regression showed that the risk signature was an independent prognostic factor for ovarian cancer patients (HR=2.58, 95%CI=2.15-3.25). Based on the risk score, the nomogram signature was successfully constructed, agreeing well with calibration curves, and the decision curve showed that it had a positive net benefits in guiding clinical decision-making. Conclusions The novel immune-related prognosis signature constructed in this study has good efficacy in predicting the prognosis of ovarian cancer, and the related genes are the potential biomarkers for immunotherapy for ovarian cancer patients.

Key words: Ovarian cancer, Bioinformatics analysis, Prognostic signature, Prognostic biomarker, TCGA

中图分类号: 

  • R711.75 R737.31