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多组学数据分析构建肿瘤微环境中宫颈癌的六个免疫相关基因预后模型。

Multi-Omics Data Analyses Construct a Six Immune-Related Genes Prognostic Model for Cervical Cancer in Tumor Microenvironment.

作者信息

Xu Fangfang, Shen Jiacheng, Xu Shaohua

机构信息

Department of Gynecology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Tongji University, Shanghai, China.

出版信息

Front Genet. 2021 May 24;12:663617. doi: 10.3389/fgene.2021.663617. eCollection 2021.

Abstract

The cross-talk between tumor cells and the tumor microenvironment (TME) is an important factor in determining the tumorigenesis and progression of cervical cancer (CC). However, clarifying the potential mechanisms which trigger the above biological processes remains a challenge. The present study focused on immune-relevant differences at the transcriptome and somatic mutation levels through an integrative multi-omics analysis based on The Cancer Genome Atlas database. The objective of the study was to recognize the specific immune-related prognostic factors predicting the survival and response to immunotherapy of patients with CC. Firstly, eight hub immune-related prognostic genes were ultimately identified through construction of a protein-protein interaction network and Cox regression analysis. Secondly, 32 differentially mutated genes were simultaneously identified based on the different levels of immune infiltration. As a result, an immune gene-related prognostic model (IGRPM), including six factors (chemokine receptor 7 [CCR7], CD3d molecule [CD3D], CD3e molecule [CD3E], and integrin subunit beta 2 [ITGB2], family with sequence similarity 133 member A [FAM133A], and tumor protein p53 [TP53]), was finally constructed to forecast clinical outcomes of CC. Its predictive capability was further assessed and validated using the Gene Expression Omnibus validation set. In conclusion, IGRPM may be a promising prognostic signature to predict the prognoses and responses to immunotherapy of patients with CC. Moreover, the multi-omics study showed that IGRPM could be a novel therapeutic target for CC, which is a promising biomarker for indicating the immune-dominant status of the TME and revealing the potential mechanisms responsible for the tumorigenesis and progression of CC.

摘要

肿瘤细胞与肿瘤微环境(TME)之间的相互作用是决定宫颈癌(CC)发生发展的重要因素。然而,阐明触发上述生物学过程的潜在机制仍然是一项挑战。本研究基于癌症基因组图谱数据库,通过综合多组学分析,聚焦于转录组和体细胞突变水平上与免疫相关的差异。该研究的目的是识别预测CC患者生存和免疫治疗反应的特定免疫相关预后因素。首先,通过构建蛋白质-蛋白质相互作用网络和Cox回归分析,最终确定了8个核心免疫相关预后基因。其次,基于不同水平的免疫浸润,同时鉴定出32个差异突变基因。结果,最终构建了一个免疫基因相关预后模型(IGRPM),包括6个因素(趋化因子受体7 [CCR7]、CD3d分子[CD3D]、CD3e分子[CD3E]、整合素亚基β2 [ITGB2]、序列相似性家族133成员A [FAM133A]和肿瘤蛋白p53 [TP53]),用于预测CC的临床结局。使用基因表达综合数据库验证集进一步评估和验证了其预测能力。总之,IGRPM可能是预测CC患者预后和免疫治疗反应的一个有前景的预后标志物。此外,多组学研究表明,IGRPM可能是CC的一个新的治疗靶点,是指示TME免疫主导状态和揭示CC发生发展潜在机制的一个有前景的生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7728/8181403/731e334df3c3/fgene-12-663617-g001.jpg

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