Development of Prognostic Features of Hepatocellular Carcinoma Based on Metabolic Gene Classification and Immune and Oxidative Stress Characteristic Analysis.
Development of Prognostic Features of Hepatocellular Carcinoma Based on Metabolic Gene Classification and Immune and Oxidative Stress Characteristic Analysis.
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基于代谢基因分类和免疫及氧化应激特征分析的肝细胞癌预后特征的发展
DOI：
10.1155/2023/1847700
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发表时间：
2023
影响因子：
--
通讯作者：
Zhang, Jian
中科院分区：
文献类型：
--
作者：
Cui, Shimeng;Zhang, Minghao;Bai, Shanshan;Bi, Yanfang;Cong, Shan;Jin, Shi;Li, Shuang;He, Hui;Zhang, Jian
以代谢基因为基础的HCC分子分型除了可以补充临床分期系统的局限性外，还可以为HCC的诊断、治疗、预后预测、免疫浸润和氧化应激提供帮助。这将有助于更好地代表HCC的更深层次特征。 TCGA数据集结合GSE 14520和HCCDB 18数据集用于确定代谢亚型（MC），使用AnchorsusperterPlus。采用ssGSEA方法计算22种不同免疫细胞的IFNγ评分、氧化应激途径评分和评分分布，并使用CIBERSORT评估其差异表达。为了生成亚型分类特征索引，使用LDA。借助WGCNA筛选代谢基因共表达模块。 鉴定了三种MC（MC 1、MC 2和MC 3），并显示出不同的能力（MC 2-较差和MC 1-较好）。虽然MC 2具有高免疫微环境浸润，但与MC 1相比，MC 2中T细胞耗竭标志物以高水平表达。大多数氧化应激相关途径在MC 2亚型中被抑制，在MC 1亚型中被激活。全癌免疫表型分析显示，预后不良的C1、C2亚型占MC 2、MC 3亚型的比例明显高于MC 1，而预后较好的C3亚型占MC 2的比例明显低于MC 1。根据TIDE分析的结果，MC 1从免疫方案中获益的可能性更大。发现MC 2对传统化疗药物具有更大的敏感性。最后，7个潜在的基因标志物指示HCC预后。 从多角度、多层次比较HCC代谢亚型间肿瘤微环境和氧化应激的差异（变化）。代谢相关的分子分型对于全面、深入地阐明HCC的分子病理学特征、探索可靠的诊断标志物、完善肿瘤分期系统、指导HCC的个体化治疗都有重要意义。
The molecular classification of HCC premised on metabolic genes might give assistance for diagnosis, therapy, prognosis prediction, immune infiltration, and oxidative stress in addition to supplementing the limitations of the clinical staging system. This would help to better represent the deeper features of HCC. TCGA datasets combined with GSE14520 and HCCDB18 datasets were used to determine the metabolic subtype (MC) using ConsensusClusterPlus. ssGSEA method was used to calculate the IFNγ score, the oxidative stress pathway scores, and the score distribution of 22 distinct immune cells, and their differential expressions were assessed with the use of CIBERSORT. To generate a subtype classification feature index, LDA was utilized. Screening of the metabolic gene coexpression modules was done with the help of WGCNA. Three MCs (MC1, MC2, and MC3) were identified and showed different prognoses (MC2-poor and MC1-better). Although MC2 had a high immune microenvironment infiltration, T cell exhaustion markers were expressed at a high level in MC2 in contrast with MC1. Most oxidative stress-related pathways are inhibited in the MC2 subtype and activated in the MC1 subtype. The immunophenotyping of pan-cancer showed that the C1 and C2 subtypes with poor prognosis accounted for significantly higher proportions of MC2 and MC3 subtypes than MC1, while the better prognostic C3 subtype accounted for significantly lower proportions of MC2 than MC1. As per the findings of the TIDE analysis, MC1 had a greater likelihood of benefiting from immunotherapeutic regimens. MC2 was found to have a greater sensitivity to traditional chemotherapy drugs. Finally, 7 potential gene markers indicate HCC prognosis. The difference (variation) in tumor microenvironment and oxidative stress among metabolic subtypes of HCC was compared from multiple angles and levels. A complete and thorough clarification of the molecular pathological properties of HCC, the exploration of reliable markers for diagnosis, the improvement of the cancer staging system, and the guiding of individualized treatment of HCC all gain benefit greatly from molecular classification associated with metabolism.
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影响因子：
7.3
作者：
Kuang Y;Sechi M;Nurra S;Ljungman M;Neamati N
通讯作者：
Neamati N
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：
5.1
作者：
McGlynn KA;Petrick JL;London WT
通讯作者：
London WT
影响因子：
13.5
作者：
Beyoglu, Diren;Imbeaud, Sandrine;Maurhofer, Olivier;Bioulac-Sage, Paulette;Zucman-Rossi, Jessica;Dufour, Jean-Francois;Idle, Jeffrey R.
通讯作者：
Idle, Jeffrey R.
影响因子：
5
作者：
Goossens N;Sun X;Hoshida Y
通讯作者：
Hoshida Y