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血管生成相关免疫特征与肝细胞癌的预后、肿瘤微环境及治疗敏感性相关。

Angiogenesis-Related Immune Signatures Correlate With Prognosis, Tumor Microenvironment, and Therapeutic Sensitivity in Hepatocellular Carcinoma.

作者信息

Yang Yuan, Wu Guozhi, Li Qiang, Zheng Ya, Liu Min, Zhou Lingshan, Chen Zhaofeng, Wang Yuping, Guo Qinghong, Ji Rui, Zhou Yongning

机构信息

The First Clinical Medical College, Lanzhou University, Lanzhou, China.

Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou, China.

出版信息

Front Mol Biosci. 2021 Jun 28;8:690206. doi: 10.3389/fmolb.2021.690206. eCollection 2021.

Abstract

Hepatocellular carcinoma (HCC) is one of the highly heterogeneous cancers that lacks an effective risk model for prognosis prediction. Therefore, we searched for angiogenesis-related immune genes that affected the prognosis of HCC to construct a risk model and studied the role of this model in HCC. In this study, we collected the transcriptome data of HCC from The Genome Atlas (TCGA) and the International Genome Consortium (ICGC) database. Pearson correlation analysis was performed to identify the association between immune genes and angiogenesis-related genes. Consensus clustering was applied to divide patients into clusters A and B. Subsequently, we studied the differentially expressed angiogenesis-related immune genes (DEari-genes) that affected the prognosis of HCC. The most significant features were identified by least absolute shrinkage and selection operator (LASSO) regression, and a risk model was constructed. The reliability of the risk model was evaluated in the TCGA discovery cohort and the ICGC validation cohort. In addition, we compared the novel risk model to the previous models based on ROC analysis. ssGSEA analysis was used for function evaluation, and pRRophetic was utilized to predict the sensitivity of administering chemotherapeutic agents. Cluster A patients had favorable survival rates. A total of 23 DEari-genes were correlated with the prognosis of HCC. A five-gene (including BIRC5, KITLG, PGF, SPP1, and SHC1) signature-based risk model was constructed. After regrouping the HCC patients by the median score, we could effectively discriminate between them based on the adverse survival outcome, the unique tumor immune microenvironment, and low chemosensitivity. The five-gene signature-based risk score established by ari-genes showed a promising clinical prediction value.

摘要

肝细胞癌(HCC)是高度异质性的癌症之一,缺乏有效的预后预测风险模型。因此,我们寻找影响HCC预后的血管生成相关免疫基因以构建风险模型,并研究该模型在HCC中的作用。在本研究中,我们从癌症基因组图谱(TCGA)和国际癌症基因组联盟(ICGC)数据库收集了HCC的转录组数据。进行Pearson相关性分析以确定免疫基因与血管生成相关基因之间的关联。应用一致性聚类将患者分为A组和B组。随后,我们研究了影响HCC预后的差异表达血管生成相关免疫基因(DEari基因)。通过最小绝对收缩和选择算子(LASSO)回归确定最显著特征,并构建风险模型。在TCGA发现队列和ICGC验证队列中评估风险模型的可靠性。此外,我们基于ROC分析将新的风险模型与先前的模型进行比较。使用单样本基因集富集分析(ssGSEA)进行功能评估,并利用pRRophetic预测化疗药物给药的敏感性。A组患者生存率良好。共有23个DEari基因与HCC的预后相关。构建了基于五个基因(包括BIRC5、KITLG、PGF、SPP1和SHC1)特征的风险模型。根据中位数评分对HCC患者重新分组后,我们可以根据不良生存结局、独特的肿瘤免疫微环境和低化疗敏感性有效地对他们进行区分。由ari基因建立的基于五个基因特征的风险评分显示出有前景的临床预测价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65e5/8273615/f1d45dfd0ef4/fmolb-08-690206-g001.jpg

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