Comprehensive analysis of complement-associated molecular features in hepatocellular carcinoma.
Comprehensive analysis of complement-associated molecular features in hepatocellular carcinoma.
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肝细胞癌补体相关分子特征综合分析
DOI：
10.3724/abbs.2022097
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发表时间：
2022-08-25
影响因子：
3.7
通讯作者：
Tang Z
中科院分区：
文献类型：
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作者：
Huang R;Zhu G;Fu X;Liu W;Tao C;Gao J;Qu W;Fang Y;Jiang X;Ding Z;Zhou J;Shi Y;Fan J;Tang Z
补体级联在人体免疫中起着“补充”作用。然而，补体系统在影响肝细胞癌（HCC）分子和临床特征中的潜在作用仍不清楚。在这项研究中，分析了 11 个公共数据集，根据 18 个经典补体相关基因比较正常样本和癌样本之间的补体状态。构建补体分数是为了量化单个肿瘤的补体特征。癌症基因组图谱 (TCGA) 队列中的 HCC 患者专注于在补体状态和免疫浸润、miRNA 表达、DNA 甲基化、临床病理特征和药物反应之间进行系统分析。结果表明，正常组织中的补体得分显着高于肿瘤组织。 TCGA 队列中的肿瘤样本分为补体评分低组和补体评分高组。通路分析表明，补体得分高的组中肿瘤促进通路通常受到抑制。这项研究还表明，在补体得分高的样本中，CD8 + T 细胞和自然杀伤细胞等肿瘤杀伤免疫细胞丰富，并且肿瘤抑制 miRNA 上调。此外，我们发现补体评分与某些临床特征呈负相关，包括病理分级、临床分期和门静脉侵犯。此外，发现各种分子特征以及补体评分与抗癌药物的反应相关。这项研究提供了全面、多维的分析，有助于理解补体在癌症中的作用。
The complement cascade plays a “complementing” role in human immunity. However, the potential roles of complement system in impacting molecular and clinical features of hepatocellular carcinoma (HCC) remain unclear. In this study, eleven public datasets are analyzed to compare the complement status between normal and cancerous samples based on 18 classical complement-associated genes. The complement scores are constructed to quantify complement signatures of individual tumors. HCC patients in the The Cancer Genome Atlas (TCGA) cohort are focused to perform systematical analyses between complement status and immune infiltration, miRNA expression, DNA methylation, clinicopathological features, and drug response. The results show that the complement scores in normal tissues are dramatically higher than those of tumor tissues. Tumor samples in the TCGA cohort are classified into complement score-low and score-high groups. Pathway analysis reveals that tumor-promoting pathways are typically inhibited in complement score-high group. This study also shows that tumor-killing immune cells, such as CD8 + T cells and natural killer cells are abundant and tumor-suppressing miRNAs are upregulated in complement score-high samples. In addition, we identify that complement scores are negatively correlated with certain clinical features, including pathological grade, clinical-stage, and portal vein invasion. Moreover, various molecular features together with complement scores are found to be correlated with response to anti-cancer drugs. This study provides a comprehensive and multidimensional analysis conducive to understanding the role of complement in cancer.
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DOI：
10.1093/jnci/djx030
发表时间：
2017-09-01
期刊：
Journal of the National Cancer Institute
影响因子：
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作者：
Jemal A;Ward EM;Johnson CJ;Cronin KA;Ma J;Ryerson B;Mariotto A;Lake AJ;Wilson R;Sherman RL;Anderson RN;Henley SJ;Kohler BA;Penberthy L;Feuer EJ;Weir HK
通讯作者：
Weir HK
影响因子：
7
作者：
Geeleher P;Zhang Z;Wang F;Gruener RF;Nath A;Morrison G;Bhutra S;Grossman RL;Huang RS
通讯作者：
Huang RS
影响因子：
3.6
作者：
Lindorfer, Margaret A.;Cook, Erika M.;Taylor, Ronald P.
通讯作者：
Taylor, Ronald P.
影响因子：
9.7
作者：
Huang, Run;Yu, Yang;Zheng, Qi
通讯作者：
Zheng, Qi
影响因子：
30.5
作者：
通讯作者：
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