Systematic Construction and Validation of a Prognostic Model for Hepatocellular Carcinoma Based on Immune-Related Genes.
Systematic Construction and Validation of a Prognostic Model for Hepatocellular Carcinoma Based on Immune-Related Genes.
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基于免疫相关基因的肝细胞癌预后模型的系统构建和验证。
DOI：
10.3389/fcell.2021.700553
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发表时间：
2021
影响因子：
5.5
通讯作者：
Han Y
中科院分区：
文献类型：
--
作者：
Yu J;Ma S;Tian S;Zhang M;Ding X;Liu Y;Yang F;Hu Y;Xuan G;Zhou X;Wang J;Han Y
肝细胞癌是一种高度侵袭性的肿瘤，具有较高的发病率和死亡率。最近，免疫疗法已被证明是一种很有前途的肝癌治疗方法。CheckMate-040或IMbrad150试验的结果证明了免疫疗法在肝癌系统治疗中的重要性。因此，本研究试图建立基于免疫相关基因(IRGS)的可靠的肝癌预后预测模型，为肝癌的免疫治疗提供新的视角。在本研究中，我们使用了包含851个肝癌样本的四个数据集，其中包括来自癌症基因组图谱(TCGA)数据库的340个具有完整临床信息的样本，以建立基于IRGS差异表达的预测肝癌患者预后的有效模型，并使用国际癌症基因组联合会(ICGC)的数据对该预后模型进行了验证。通过蛋白质-蛋白质相互作用(PPI)网络分析，筛选出MMP9、FOS、CAT、ESR1、Angptl3和KLKB1等6个最具代表性的IRGS进行进一步研究。此外，我们评估了六种特征的IRGS与肿瘤免疫微环境、临床分期和抗癌药物敏感性的相关性。我们还探索了特征IRGS的差异表达是否是肝细胞癌特有的，还是存在于泛癌中。6种特征IRGS在大多数肿瘤组织和癌旁正常组织中的表达水平差异有统计学意义。此外，这些特征性的IRG与肝细胞癌患者的免疫细胞浸润有很强的相关性。我们发现MMP9和ESR1是影响肝癌预后的独立因素，而CAT、ESR1和KLKB1则与临床分期有关。我们收集了来自西京医院的24例肝癌患者的石蜡切片，以确定这五个基因(MMP9、ESR1、CAT、FOS和KLKB1)的差异表达。最后，决策曲线分析(DCA)和诺模图的结果显示，我们的模型为大多数肝癌患者提供了预后益处，预测的总生存期(OS)与实际OS一致。总之，我们系统地构建了一个新的预后模型，为肝癌提供了新的见解。
Hepatocellular carcinoma (HCC), a highly aggressive tumor, has high incidence and mortality rates. Recently, immunotherapies have been shown to be a promising treatment in HCC. The results of either the CheckMate-040 or IMbrave 150 trials demonstrate the importance of immunotherapy in the systemic treatment of liver cancer. Thus, in this study, we tried to establish a reliable prognostic model for liver cancer based on immune-related genes (IRGs) and to provide a new insight for immunotherapy of HCC. In this study, we used four datasets that incorporated 851 HCC samples, including 340 samples with complete clinical information from the cancer genome atlas (TCGA) database, to establish an effective model for predicting the prognosis of HCC patients based on the differential expression of IRGs and validated the prognostic model using the data from International Cancer Genome Consortium (ICGC). The top 6 characteristic IRGs identified by protein-protein interaction (PPI) network analysis, MMP9, FOS, CAT, ESR1, ANGPTL3, and KLKB1, were selected for further study. In addition, we assessed the correlations of the six characteristic IRGs with the tumor immune microenvironment, clinical stage, and sensitivity to anti-cancer drugs. We also explored whether the differential expression of the characteristic IRGs was specific to HCC or present in pan-cancer. The expression levels of the six characteristic IRGs were significantly different between most tumor tissues and adjacent normal tissues. In addition, these characteristic IRGs showed a strong association with immune cell infiltration in HCC patients. We found that MMP9 and ESR1 were independent prognostic factors for HCC, while CAT, ESR1, and KLKB1 were associated with the clinical stage. We collected HCC paraffin sections from 24 patients from Xijing hospital to identify the differential expression of the five genes (MMP9, ESR1, CAT, FOS, and KLKB1). Finally, the results of decision curve analysis (DCA) and nomogram revealed that our models provided a prognostic benefit for most HCC patients and the predicted overall survival (OS) was consistent with the actual OS. In conclusion, we systemically constructed a novel prognostic model that provides new insights into HCC.
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影响因子：
14
作者：
Kang, Soo-Jin;Cho, Young-Rak;Park, Seung-Jung
通讯作者：
Park, Seung-Jung
影响因子：
13.5
作者：
Giannini, Edoardo G.;Farinati, Fabio;Trevisani, Franco
通讯作者：
Trevisani, Franco
影响因子：
64.5
作者：
Lewis, BP;Shih, IH;Burge, CB
通讯作者：
Burge, CB
影响因子：
5.2
作者：
Hishida, Mitsuhiro;Nomoto, Shuji;Kodera, Yasuhiro
通讯作者：
Kodera, Yasuhiro
影响因子：
12.3
作者：
Li B;Severson E;Pignon JC;Zhao H;Li T;Novak J;Jiang P;Shen H;Aster JC;Rodig S;Signoretti S;Liu JS;Liu XS
通讯作者：
Liu XS