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肝细胞癌(HCC)肿瘤微环境中预后免疫相关基因的综合分析。

Comprehensive analysis of prognostic immune-related genes in the tumor microenvironment of hepatocellular carcinoma (HCC).

机构信息

Department of Gastroenterology, The Affiliated People's Hospital of Ningbo University, Zhejiang Province, China.

出版信息

Medicine (Baltimore). 2021 Oct 1;100(39):e27332. doi: 10.1097/MD.0000000000027332.

Abstract

Growing evidence supports that the tumor microenvironment plays a key role in the development and progression of tumors. But immune microenvironment of hepatocellular carcinoma (HCC) has not yet been fully explored. In the present investigation, the clinical value and prognostic significance of immune-related genes in HCC were investigated.The immune and stromal scores of HCC were calculated through the application of Estimation of Stromal and Immune cells in Malignant Tumor tissues using Expression data Algorithm based on the Cancer Genome Atlas database. Differentially expressed genes were identified using the "edgeR" package of the R software. Functional annotation and pathway enrichment were performed using "ggplots2" and "clusterProfiler" packages in R software. Protein-protein interaction network was constructed using STRING, and the hub genes were identified through the Cytoscape. Survival analysis was performed using Kaplan-Meier methods. Tumor Immune Estimation Resource algorithm was used to view the immune landscape of the microenvironment in HCC.Firstly, the immune and stromal scores of HCC were calculated and we found that the immune and stromal scores of HCC were closely related to the patients' prognosis. Then the differentially expressed genes were identified respectively stratified by the median value of the immune and stromal scores, and the immune-related genes that related to the prognosis in HCC patients were further identified. Functional enrichment analysis and protein-protein interaction networks further showed that these genes mainly participated in immune-related biological process. In addition, dendritic cells were found to be the most abundant in the microenvironment of HCC through Tumor Immune Estimation Resource algorithm and were significantly associated with the patients' prognosis. To robust the results, the immune-related genes were validated in an independent dataset from the Gene Expression Omnibus database.We arrived at a more comprehensive understanding of the microenvironment of HCC and extracted 7 immune-related genes that were significantly associated with the recurrence survival of HCC.

摘要

越来越多的证据表明,肿瘤微环境在肿瘤的发生和发展中起着关键作用。但是,肝癌的免疫微环境尚未得到充分探索。在本研究中,我们研究了免疫相关基因在肝癌中的临床价值和预后意义。通过应用基于癌症基因组图谱数据库的基于表达数据的算法估计肿瘤组织中的基质和免疫细胞,计算了肝癌的免疫和基质评分。使用 R 软件中的“edgeR”包鉴定差异表达基因。使用 R 软件中的“ggplots2”和“clusterProfiler”包进行功能注释和通路富集。使用 STRING 构建蛋白质-蛋白质相互作用网络,并通过 Cytoscape 识别枢纽基因。使用 Kaplan-Meier 方法进行生存分析。使用 Tumor Immune Estimation Resource 算法观察 HCC 微环境的免疫景观。首先,计算了 HCC 的免疫和基质评分,我们发现 HCC 的免疫和基质评分与患者的预后密切相关。然后,分别根据免疫和基质评分的中位数对差异表达基因进行分层鉴定,并进一步鉴定与 HCC 患者预后相关的免疫相关基因。功能富集分析和蛋白质-蛋白质相互作用网络进一步表明,这些基因主要参与免疫相关的生物学过程。此外,通过 Tumor Immune Estimation Resource 算法发现,树突状细胞在 HCC 的微环境中最为丰富,并且与患者的预后显著相关。为了验证结果,我们在来自 Gene Expression Omnibus 数据库的独立数据集上验证了免疫相关基因。我们对 HCC 的微环境有了更全面的了解,并提取了 7 个与 HCC 复发生存显著相关的免疫相关基因。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52fe/8483847/bedcc17be26d/medi-100-e27332-g001.jpg

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