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鉴定和验证与糖酵解相关的多组学生存预后模型用于肝细胞癌。

Identification and validation of a glycolysis-associated multiomics prognostic model for hepatocellular carcinoma.

机构信息

Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.

Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.

出版信息

Aging (Albany NY). 2021 Mar 3;13(5):7481-7498. doi: 10.18632/aging.202613.

Abstract

Increased glycolysis has been reported as a major metabolic hallmark in many cancers, and is closely related to malignant behavior of tumors. However, the potential mechanism of glycolysis in hepatocellular carcinoma (HCC) and its prognostic value are not well understood. To address this, we investigated glycolysis-related gene expression data of patients with HCC from TCGA and ICGC. Patients were categorized into three different glycolysis-associated subgroups: Glycolysis-M, Glycolysis-H, and Glycolysis-L. We found that Glycolysis-H combined with Glycolysis-M (Glycolysis-H+M) subgroup was associated with poor overall survival and distinct cancer stem cell characteristics and immune infiltrate patterns. Additionally, multiomics-based analyses were conducted to evaluate genomic patterns of glycolysis subgroups, including their gene mutations, copy number variations, and RNA-sequencing data. Finally, a glycolysis-associated multiomics prognostic model (GMPM) consisting of 19 glycolysis-associated genes was developed. The capability of GMPM in categorizing patients with HCC into high- and low-risk groups was validated with independent HCC datasets. Finally, GMPM was confirmed as an independent risk factor for the prognosis of patients with HCC. We believe that our findings provide new insights into the mechanism of glycolysis and highlight the potential clinical value of GMPM in predicting the prognosis of patients with HCC.

摘要

已有报告显示,糖酵解增加是许多癌症的主要代谢特征,与肿瘤的恶性行为密切相关。然而,肝癌(HCC)中糖酵解的潜在机制及其预后价值尚不清楚。为了解决这个问题,我们研究了来自 TCGA 和 ICGC 的 HCC 患者的糖酵解相关基因表达数据。患者被分为三个不同的糖酵解相关亚组:糖酵解-M、糖酵解-H 和糖酵解-L。我们发现糖酵解-H 与糖酵解-M 相结合(Glycolysis-H+M)亚组与总生存期不良以及明显的癌症干细胞特征和免疫浸润模式相关。此外,我们还进行了基于多组学的分析,以评估糖酵解亚组的基因组模式,包括基因突变、拷贝数变异和 RNA 测序数据。最后,开发了一个由 19 个糖酵解相关基因组成的糖酵解相关多组学预后模型(GMPM)。使用独立的 HCC 数据集验证了 GMPM 将 HCC 患者分为高风险和低风险组的能力。最后,GMPM 被确认为 HCC 患者预后的独立危险因素。我们相信,我们的研究结果为糖酵解的机制提供了新的见解,并强调了 GMPM 在预测 HCC 患者预后方面的潜在临床价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe54/7993684/5cb81e0952b8/aging-13-202613-g002.jpg

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