Analysis of the Heterogeneity of the Tumor Microenvironment and the Prognosis and Immunotherapy Response of Different Immune Subtypes in Hepatocellular Carcinoma.
Analysis of the Heterogeneity of the Tumor Microenvironment and the Prognosis and Immunotherapy Response of Different Immune Subtypes in Hepatocellular Carcinoma.
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DOI：
10.1155/2022/1087399
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发表时间：
2022
影响因子：
--
通讯作者：
Wang X
中科院分区：
文献类型：
--
作者：
Hu J;Mao F;Li L;Wang X;Cai D;He L;Wu Q;Wang C;Zhang N;Ma Y;Wu X;Qu K;Wang X
目前的肝细胞癌临床分类不能很好地预测患者对治疗方案的可能反应，也不能预测患者的预后。我们利用肝细胞癌患者的基因表达谱来揭示肝细胞癌的异质性，并分析不同免疫亚型在预后和免疫治疗反应上的差异。首先，利用TCGA的肝细胞癌表达谱数据，结合单样本基因集浓缩分析(SsGSEA)算法，分析患者肿瘤微环境的免疫浓缩情况。随后，利用谱聚类算法提取不同的分类，将队列中的肝细胞癌分为3个亚型，并建立免疫亚型与临床特征和生存预后的相关性。患者的风险指数通过预后预测模型得到，提示风险指数与各种类型的免疫细胞之间存在相关性。我们可以将肝癌队列分为三种亚型：基质细胞激活的免疫增强型(A-IS)、一般免疫增强型(N-IS)和非免疫增强型(Non-IS)。喉癌A-IS组的3年生存率高于N-IS组和非IS组，三组间差异有统计学意义(P=0.017)。ICGC的A-IS组和N-IS组的3年生存率高于非IS组。风险指数与免疫细胞的相关性分析表明，患者的疾病风险与肿瘤相关成纤维细胞(CAF)刺激细胞、激活的基质细胞和抗PD-1抵抗细胞呈显著正相关。肝细胞癌患者肿瘤基因表达特征可作为临床分型的依据。不同的免疫亚型与生存预后密切相关。患者不同的免疫细胞状态可能会导致不同的疾病风险水平。这为肝细胞癌的临床识别和预后预测提供了重要参考。
The current clinical classification of hepatocellular carcinoma (HCC) cannot well predict the patient's possible response to the treatment plan, nor can it predict the patient's prognosis. We use the gene expression patterns of patients with hepatocellular carcinoma to reveal the heterogeneity of hepatocellular carcinoma and analyze the differences in prognosis and immunotherapy response of different immune subtypes. Firstly, using the hepatocellular carcinoma expression profile data of TCGA, combined with the single sample gene set enrichment analysis (ssGSEA) algorithm, the immune enrichment of the patient's tumor microenvironment was analyzed. Subsequently, the spectral clustering algorithm was used to extract different classifications, and the cohort of hepatocellular carcinoma was divided into 3 subtypes, and the correlation between immune subtypes and clinical characteristics and survival prognosis was established. The patient's risk index is obtained through the prognostic prediction model, suggesting the correlation between the risk index and various types of immune cells. We can divide the liver cancer cohort into three subtypes: stromal cell activated immune-enriched type (A-IS), general immune-enriched type (N-IS), and non-immune-enriched type (non-IS). The 3-year survival rate of TCGA's A-IS is higher than that of N-IS and non-IS, and the three components are significantly different (p = 0.017). The 3-year survival rates of ICGC's A-IS and N-IS groups were higher than those of the non-IS group. The analysis of the correlation between the risk index and immune cells showed that the patient's disease risk was significantly positively correlated with cancer-associated fibroblast (CAF) stimulated cell, activated stroma cell, and anti-PD-1 resistant cell. The tumor gene expression characteristics of patients with hepatocellular carcinoma can be used as a basis for clinical patient classification. Different immune subtypes are closely related to survival prognosis. Different immune cell states of patients may lead to different disease risk levels. All these provide important references for the clinical identification and prognosis prediction of hepatocellular carcinoma.
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影响因子：
64.5
作者：
Cancer Genome Atlas Research Network. Electronic address: wheeler@bcm.edu;Cancer Genome Atlas Research Network
通讯作者：
Cancer Genome Atlas Research Network
影响因子：
64.5
作者：
Cancer Genome Atlas Research Network
通讯作者：
Cancer Genome Atlas Research Network
影响因子：
17.1
作者：
Allen E;Jabouille A;Rivera LB;Lodewijckx I;Missiaen R;Steri V;Feyen K;Tawney J;Hanahan D;Michael IP;Bergers G
通讯作者：
Bergers G
影响因子：
11.4
作者：
Giordano, Marilyn;Henin, Coralie;Verdeil, Gregory
通讯作者：
Verdeil, Gregory
影响因子：
5.6
作者：
Chan, Anthony W. H.;Tong, Joanna H. M.;To, Ka-Fai
通讯作者：
To, Ka-Fai