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透明细胞肾细胞癌中的免疫浸润格局及其意义

Immune Infiltration Landscape in Clear Cell Renal Cell Carcinoma Implications.

作者信息

Wang Yongfeng, Yin Ci, Geng Lele, Cai Weiyang

机构信息

Department of Gynecology and Obstetrics, Yangpu Hospital, Tongji University School of Medicine, Shanghai, China.

Department of Neonatology, Shaanxi Provincial People's Hospital, Xi'an, China.

出版信息

Front Oncol. 2021 Feb 16;10:491621. doi: 10.3389/fonc.2020.491621. eCollection 2020.

Abstract

The malignant phenotypes of cancer are defined not only by its intrinsic tumor cells but also by the tumor infiltrating immune cells (TIICs) recruited to the cancer microenvironment. Clear cell renal cell carcinoma (ccRCC) immune microenvironment plays an important role in the tumorigenesis. This research investigated the characteristics of immune cell invasion of renal cell carcinoma and provided clues for future clinical implementation. Retrospectively, ccRCC gene expression was analyzed with appropriate clinicopathological data from the Cancer Genome Atlas (TCGA) and GEO database up to December 2019. The CIBERSORT algorithm, meta-analysis, principal component analysis (PCA), Single-Sample Gene Set Enrichment Analysis (ssGSEA) and hierarchical agglomerative clustering were used to measure and evaluate the respective proportions of 22 cell types of immune infiltration using normalized gene expression data. We also focused on evaluating the association with TIICs subpopulations and clinical features and molecular subtypes. TIICs subpopulation, especially Macrophages subgroup, T follicular helper (Tfh) cells and CD8 T cells, all contribute to tumorigenesis. Unsupervised clustering analysis revealed that there existed two distinct TIICs subgroups with different survival patterns. TIICs are extensively involved in the pathogenesis and development of the ccRCC. Characterizing the composition of TIICs influences the metabolism of tumors, activity, level, stage, and survival of patients. Collectively, the TIIC analysis has the potential to assist in the assessment and selection of ccRCC prognosis and treatment.

摘要

癌症的恶性表型不仅由其内在的肿瘤细胞决定,还由募集到癌症微环境中的肿瘤浸润免疫细胞(TIICs)决定。透明细胞肾细胞癌(ccRCC)免疫微环境在肿瘤发生中起重要作用。本研究调查了肾细胞癌免疫细胞浸润的特征,并为未来的临床应用提供线索。回顾性地分析了截至2019年12月来自癌症基因组图谱(TCGA)和GEO数据库的ccRCC基因表达及适当的临床病理数据。使用CIBERSORT算法、荟萃分析、主成分分析(PCA)、单样本基因集富集分析(ssGSEA)和层次聚类分析,利用标准化基因表达数据来测量和评估22种免疫浸润细胞类型的各自比例。我们还着重评估了与TIICs亚群、临床特征及分子亚型的关联。TIICs亚群,尤其是巨噬细胞亚群、滤泡辅助性T(Tfh)细胞和CD8 T细胞,均对肿瘤发生有作用。无监督聚类分析显示存在两种具有不同生存模式的TIICs亚组。TIICs广泛参与ccRCC的发病机制和发展。表征TIICs的组成会影响肿瘤的代谢、活性、分期以及患者的生存情况。总体而言,TIIC分析有潜力协助评估和选择ccRCC的预后及治疗方案。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d5d8/7923891/5451d28eb903/fonc-10-491621-g001.jpg

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