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基于 mRNA 表达和全基因组拷贝数变异鉴定宫颈癌生存特征。

Identifying a cervical cancer survival signature based on mRNA expression and genome-wide copy number variations.

机构信息

Liuzhou Maternity and Child Healthcare Hospital, Liuzhou 545001, China.

Affiliated Maternity Hospital and Affiliated Children's Hospital of Guangxi University of Science and Technology, Liuzhou 545001, China.

出版信息

Exp Biol Med (Maywood). 2022 Feb;247(3):207-220. doi: 10.1177/15353702211053580. Epub 2021 Oct 21.

Abstract

Cervical cancer mortality is the second highest in gynecological cancers. This study developed a new model based on copy number variation data and mRNA data for overall survival prediction of cervical cancer. Differentially expressed genes from The Cancer Genome Atlas dataset detected by univariate Cox regression analysis were further simplified to six by least absolute shrinkage and selection operator (Lasso) and stepwise Akaike information criterion (stepAIC). The study developed a six-gene signature, which was further verified in independent dataset. Association between immune infiltration and risk score was investigated by immune score. The relation between the signature and functional pathways was examined by gene set enrichment analysis. Ninety-nine differentially expressed genes were detected, and , , , , , and were identified as key genes to construct a six-gene signature. The prognostic signature showed a significant correlation with overall survival (hazard ratio, HR = 3.45, 95% confidence interval (CI) = 2.08-5.72, <0.00001). Immune score showed a negative correlation with the risk score calculated by the signature (<0.05). Four immune-related pathways were closely associated with risk score (<0.0001). The six-gene prognostic signature was an effective tool to predict overall survival of cervical cancer. In conclusion, the newly identified six genes may be considered as new drug targets for cervical cancer treatment.

摘要

宫颈癌死亡率在妇科癌症中位居第二。本研究基于拷贝数变异数据和 mRNA 数据,建立了一个新的模型,用于预测宫颈癌的总生存期。通过单变量 Cox 回归分析从癌症基因组图谱数据集检测到的差异表达基因,通过最小绝对值收缩和选择算子(Lasso)和逐步 Akaike 信息准则(stepAIC)进一步简化为 6 个。该研究开发了一个六基因特征,在独立数据集得到进一步验证。通过免疫评分研究了免疫浸润与风险评分之间的关系。通过基因集富集分析检验了特征与功能途径之间的关系。检测到 99 个差异表达基因, 、 、 、 、 和 被鉴定为构建六基因特征的关键基因。该预后特征与总生存期显著相关(风险比,HR=3.45,95%置信区间(CI)=2.08-5.72,<0.00001)。免疫评分与由特征计算的风险评分呈负相关(<0.05)。四个与免疫相关的途径与风险评分密切相关(<0.0001)。六基因预后特征是预测宫颈癌总生存期的有效工具。总之,新鉴定的六个基因可能被认为是宫颈癌治疗的新药物靶点。

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