HCC subtypes based on the activity changes of immunologic and hallmark gene sets in tumor and nontumor tissues
HCC subtypes based on the activity changes of immunologic and hallmark gene sets in tumor and nontumor tissues
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HCC 亚型基于肿瘤和非肿瘤组织中免疫学和标志基因集的活性变化。
DOI：
10.1093/bib/bbaa427
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发表时间：
2021-01-30
影响因子：
9.5
通讯作者：
Hu, Bo
中科院分区：
文献类型：
--
作者：
Gong, Jiao;Li, Rong;Hu, Bo
癌旁非肿瘤组织在肝细胞癌患者中的预后作用尚不清楚。肝癌切除等治疗措施后，邻近非肿瘤组织中免疫学和标志性基因的活性变化可能通过影响肝细胞的增殖和循环中肿瘤细胞的定植而对预后产生重要影响。我们的目标是根据肿瘤和非肿瘤组织中基因集的活性变化来确定肝癌的亚型和预后基因集，以改善患者的预后。我们通过基因集变异分析(GSVA)全面揭示了肝癌和非肿瘤组织中免疫学和标志性基因集的活性变化，并用非负矩阵分解法(NMF)确定了三种临床相关的肝癌亚型。亚型1的患者总体生存率较好，而亚型2和亚型3的患者预后较差。验证组中亚型为1的患者也倾向于活得更长。我们还用最小绝对收缩选择算子方法(LASSO)确定了肿瘤中的3个预后基因集和非肿瘤中的4个预后基因集。有趣的是，功能丰富分析表明，在非肿瘤组织中，四个基因集的基因与免疫反应、细胞黏附相关，而在肿瘤组织中，三个基因集的基因与细胞周期密切相关。我们的结果为准确评估预后提供了新的见解--肿瘤和邻近非肿瘤组织中基因集的重要作用，提示在选择肝癌治疗方式时，也应该考虑肿瘤和非肿瘤组织的变化，特别是在肝切除后。
The prognostic role of adjacent nontumor tissue in hepatocellular carcinoma (HCC) patients is still not clear. The activity changes of immunologic and hallmark gene sets in adjacent nontumor tissues may substantially impact on prognosis by affecting proliferation of liver cells and colonization of circulating tumor cells after HCC treatment measures such as hepatectomy. We aimed to identify HCC subtypes and prognostic gene sets based on the activity changes of gene sets in tumor and nontumor tissues, to improve patient outcomes. We comprehensively revealed the activity changes of immunologic and hallmark gene sets in HCC and nontumor samples by gene set variation analysis (GSVA), and identified three clinically relevant subtypes of HCC by nonnegative matrix factorization method (NMF). Patients with subtype 1 had good overall survival, whereas those with subtype 2 and subtype 3 had poor prognosis. Patients with subtype 1 in the validation group also tended to live longer. We also identified three prognostic gene sets in tumor and four prognostic gene sets in nontumor by least absolute shrinkage and selection operator method (LASSO). Interestingly, functional enrichment analysis revealed that in nontumor tissues, genes from four gene sets correlated with immune reaction, cell adhesion, whereas in tumor tissue, genes from three gene sets closely correlated with cell cycle. Our results offer new insights on accurately evaluating prognosis-the important role of gene sets in both tumor and adjacent nontumor tissues, suggesting that when selecting for HCC treatment modality, changes in tumor and nontumor tissues should also be considered, especially after hepatectomy.