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免疫基因组学鉴定预测宫颈癌患者的预后。

Immunogenomic Identification for Predicting the Prognosis of Cervical Cancer Patients.

机构信息

Department of Obstetrics and Gynecology, University Hospital, LMU Munich, 80377 Munich, Germany.

Klinik für Innere Medizin I, Technische Universität München, 80333 Munich, Germany.

出版信息

Int J Mol Sci. 2021 Feb 28;22(5):2442. doi: 10.3390/ijms22052442.

Abstract

Cervical cancer is primarily caused by the infection of high-risk human papillomavirus (hrHPV). Moreover, tumor immune microenvironment plays a significant role in the tumorigenesis of cervical cancer. Therefore, it is necessary to comprehensively identify predictive biomarkers from immunogenomics associated with cervical cancer prognosis. The Cancer Genome Atlas (TCGA) public database has stored abundant sequencing or microarray data, and clinical data, offering a feasible and reliable approach for this study. In the present study, gene profile and clinical data were downloaded from TCGA, and the Immunology Database and Analysis Portal (ImmPort) database. Wilcoxon-test was used to compare the difference in gene expression. Univariate analysis was adopted to identify immune-related genes (IRGs) and transcription factors (TFs) correlated with survival. A prognostic prediction model was established by multivariate cox analysis. The regulatory network was constructed and visualized by correlation analysis and Cytoscape, respectively. Gene functional enrichment analysis was performed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). A total of 204 differentially expressed IRGs were identified, and 22 of them were significantly associated with the survival of cervical cancer. These 22 IRGs were actively involved in the JAK-STAT pathway. A prognostic model based on 10 IRGs (, , , , , , , , , and ) performed moderately and steadily in squamous cell carcinoma (SCC) patients with FIGO stage I, regardless of the age and grade. Taken together, a risk score model consisting of 10 novel genes capable of predicting survival in SCC patients was identified. Moreover, the regulatory network of IRGs associated with survival (SIRGs) and their TFs provided potential molecular targets.

摘要

宫颈癌主要由高危型人乳头瘤病毒(hrHPV)感染引起。此外,肿瘤免疫微环境在宫颈癌的发生发展中起着重要作用。因此,有必要从与宫颈癌预后相关的免疫基因组学中全面鉴定预测性生物标志物。癌症基因组图谱(TCGA)公共数据库存储了丰富的测序或微阵列数据以及临床数据,为这项研究提供了可行可靠的方法。本研究从 TCGA 和免疫数据库和分析门户(ImmPort)数据库下载了基因谱和临床数据。采用 Wilcoxon 检验比较基因表达的差异。采用单因素分析鉴定与生存相关的免疫相关基因(IRGs)和转录因子(TFs)。采用多变量 cox 分析建立预后预测模型。通过相关性分析和 Cytoscape 分别构建和可视化调控网络。通过基因本体(GO)和京都基因与基因组百科全书(KEGG)进行基因功能富集分析。共鉴定出 204 个差异表达的 IRGs,其中 22 个与宫颈癌的生存显著相关。这 22 个 IRGs积极参与 JAK-STAT 通路。基于 10 个 IRGs(、、、、、、、、和)构建的预后模型在 FIGO 分期为 I 期的鳞癌(SCC)患者中表现出中等且稳定的性能,与年龄和分级无关。总之,鉴定了一个由 10 个新基因组成的风险评分模型,能够预测 SCC 患者的生存情况。此外,与生存相关的 IRGs(SIRGs)及其 TFs 的调控网络提供了潜在的分子靶点。

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