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基于免疫浸润相关基因和临床信息的卵巢癌稳健预后模型。

Robust prognostic model based on immune infiltration-related genes and clinical information in ovarian cancer.

机构信息

Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China.

Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.

出版信息

J Cell Mol Med. 2022 Jul;26(13):3659-3674. doi: 10.1111/jcmm.17360. Epub 2022 Jun 23.

Abstract

Immune infiltration of ovarian cancer (OV) is a critical factor in determining patient's prognosis. Using data from TCGA and GTEx database combined with WGCNA and ESTIMATE methods, 46 genes related to OV occurrence and immune infiltration were identified. Lasso and multivariate Cox regression were applied to define a prognostic score (IGCI score) based on 3 immune genes and 3 types of clinical information. The IGCI score has been verified by K-M curves, ROC curves and C-index on test set. In test set, IGCI score (C-index = 0.630) is significantly better than AJCC stage (C-index = 0.541, p < 0.05) and CIN25 (C-index = 0.571, p < 0.05). In addition, we identified key mutations to analyse prognosis of patients and the process related to immunity. Chi-squared tests revealed that 6 mutations are significantly (p < 0.05) related to immune infiltration: BRCA1, ZNF462, VWF, RBAK, RB1 and ADGRV1. According to mutation survival analysis, we found 5 key mutations significantly related to patient prognosis (p < 0.05): CSMD3, FLG2, HMCN1, TOP2A and TRRAP. RB1 and CSMD3 mutations had small p-value (p < 0.1) in both chi-squared tests and survival analysis. The drug sensitivity analysis of key mutation showed when RB1 mutation occurs, the efficacy of six anti-tumour drugs has changed significantly (p < 0.05).

摘要

卵巢癌 (OV) 的免疫浸润是决定患者预后的关键因素。本研究结合 TCGA 和 GTEx 数据库,利用 WGCNA 和 ESTIMATE 方法,鉴定出与 OV 发生和免疫浸润相关的 46 个基因。通过 Lasso 和多变量 Cox 回归,基于 3 个免疫基因和 3 种临床信息,定义了一个预后评分 (IGCI 评分)。通过 K-M 曲线、ROC 曲线和测试集中的 C 指数验证了 IGCI 评分。在测试集中,IGCI 评分 (C 指数 = 0.630) 明显优于 AJCC 分期 (C 指数 = 0.541, p < 0.05) 和 CIN25 (C 指数 = 0.571, p < 0.05)。此外,我们还鉴定了关键突变,以分析患者的预后和与免疫相关的过程。卡方检验显示,6 个突变与免疫浸润显著相关 (p < 0.05):BRCA1、ZNF462、VWF、RBAK、RB1 和 ADGRV1。根据突变生存分析,我们发现 5 个关键突变与患者预后显著相关 (p < 0.05):CSMD3、FLG2、HMCN1、TOP2A 和 TRRAP。RB1 和 CSMD3 的突变在卡方检验和生存分析中均具有较小的 p 值 (p < 0.1)。关键突变的药物敏感性分析表明,当 RB1 突变发生时,六种抗肿瘤药物的疗效发生了显著变化 (p < 0.05)。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc00/9258710/9f4605a679e4/JCMM-26-3659-g007.jpg

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