Identification and Characterization of Robust Hepatocellular Carcinoma Prognostic Subtypes Based on an Integrative Metabolite-Protein Interaction Network.
Identification and Characterization of Robust Hepatocellular Carcinoma Prognostic Subtypes Based on an Integrative Metabolite-Protein Interaction Network.
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DOI：
10.1002/advs.202100311
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发表时间：
2021-09
期刊：
影响因子：
--
通讯作者：
Piao HL
中科院分区：
文献类型：
--
作者：
Chen D;Zhang Y;Wang W;Chen H;Ling T;Yang R;Wang Y;Duan C;Liu Y;Guo X;Fang L;Liu W;Liu X;Liu J;Otkur W;Qi H;Liu X;Xia T;Liu HX;Piao HL
代谢物-蛋白质相互作用（MPI）在癌症代谢中起着关键作用。然而，由于癌细胞的复杂性，我们目前对癌症中MPI的了解仍然有限。在此，作者构建了一个集成的MPI网络，并提出了一个基于MPI网络的肝细胞癌（HCC）亚型和机制探索工作流程。基于MPI网络上枢纽蛋白的表达，鉴定了两种预后不同的HCC亚型。与此同时，观察到预后不良亚型的多种相互依赖的特征，包括缺氧、代谢途径的DNA高甲基化、脂肪酸积累、免疫途径上调和疲惫的T细胞浸润。值得注意的是，免疫途径上调可能是由累积的不饱和脂肪酸诱导的，这些脂肪酸预计与多种免疫调节剂如SRC和TGFB 1相互作用。此外，基于肿瘤微环境组成，预后不良亚型进一步分为两个亚群，显示代谢的显著差异。该亚型在多个HCC队列（包括早期HCC）中显示出很强的一致性。总体而言，作者重新定义了HCC预后亚型，并确定了将代谢与免疫调节联系起来的潜在MPI，从而促进了对HCC代谢异质性的理解和临床应用。作者构建了一个综合代谢物-蛋白质相互作用（MPI）网络，并开发了MPI预测模型。MPI网络有助于重新定义可靠的肝细胞癌预后亚型。各亚型在缺氧、代谢酶DNA甲基化、免疫途径、脂肪酸积累以及肿瘤微环境等方面存在显著差异。同时，不饱和脂肪酸是代谢和免疫调节之间的潜在联系。
Metabolite‐protein interactions (MPIs) play key roles in cancer metabolism. However, our current knowledge about MPIs in cancers remains limited due to the complexity of cancer cells. Herein, the authors construct an integrative MPI network and propose a MPI network based hepatocellular carcinoma (HCC) subtyping and mechanism exploration workflow. Based on the expressions of hub proteins on the MPI network, two prognosis‐distinctive HCC subtypes are identified. Meanwhile, multiple interdependent features of the poor prognostic subtype are observed, including hypoxia, DNA hypermethylation of metabolic pathways, fatty acid accumulation, immune pathway up‐regulation, and exhausted T‐cell infiltration. Notably, the immune pathway up‐regulation is probably induced by accumulated unsaturated fatty acids which are predicted to interact with multiple immune regulators like SRC and TGFB1. Moreover, based on tumor microenvironment compositions, the poor prognostic subtype is further divided into two sub‐populations showing remarkable differences in metabolism. The subtyping shows a strong consistency across multiple HCC cohorts including early‐stage HCC. Overall, the authors redefine robust HCC prognosis subtypes and identify potential MPIs linking metabolism to immune regulations, thus promoting understanding and clinical applications about HCC metabolism heterogeneity. The authors construct an integrative metabolite‐protein interaction (MPI) network and develop a MPI prediction model. The MPI network helps redefine robust hepatocellular carcinoma prognostic subtypes. The subtypes show remarkable differences in hypoxia, DNA methylation of metabolic enzymes, immune pathways, fatty acid accumulation as well as tumor microenvironment. Meanwhile, unsaturated fatty acids are potential links between the metabolism and immune regulations.
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影响因子：
4
作者：
Liu ST;Pham H;Pandol SJ;Ptasznik A
通讯作者：
Ptasznik A
影响因子：
46.9
作者：
通讯作者：
--
T细胞共刺激和共抑制的分子机制。
DOI：
10.1038/nri3405
发表时间：
2013-04
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
影响因子：
29
作者：
Pavlova NN;Thompson CB
通讯作者：
Thompson CB
影响因子：
19
作者：
Ackerman, Daniel;Simon, M. Celeste
通讯作者：
Simon, M. Celeste