Identification of a glycolysis-related gene signature for predicting prognosis in patients with hepatocellular carcinoma.
Identification of a glycolysis-related gene signature for predicting prognosis in patients with hepatocellular carcinoma.
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DOI：
10.1186/s12885-022-09209-9
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发表时间：
2022-02-05
期刊：
影响因子：
3.8
通讯作者：
Liu J
中科院分区：
文献类型：
--
作者：
Kong J;Yu G;Si W;Li G;Chai J;Liu Y;Liu J
肝细胞癌是世界上最常见的原发性肝癌。尽管HCC的诊断和治疗取得了很大进展，但由于肿瘤发生发展的复杂机制，HCC的预后仍然令人沮丧。最近的研究表明，沃伯格效应与各种癌症的发生、进展和治疗有关；然而，关于糖酵解与HCC预后关系的探讨较少。从公共数据库下载mRNA表达谱。采用基因集富集分析（GSEA）探索糖酵解相关基因（GRGs），采用LASSO法和Cox回归分析鉴定与HCC预后相关的GRGs，构建与总生存期（OS）和无病生存期（DFS）相关的预测模型。探讨该预测模型与肿瘤突变负荷（TMB）和肿瘤免疫微环境（TIME）的关系。最后，采用real-time PCR验证临床样品和不同细胞系中GRGs的表达水平。鉴定出5个GRGs （ABCB6、ANKZF1、B3GAT3、KIF20A和STC2）并用于构建预测HCC OS和DFS的基因特征。使用中位数将HCC患者分为低危组和高危组。高危组患者的OS/DFS较低风险组患者差，与较高的TMB相关，并与较高的CD4+记忆T细胞静息率和CD4+记忆T细胞活化率相关。最后，real-time PCR显示，与邻近的正常样本相比，HCC样本中这5种GRGs都出现了失调。我们确定了5个与HCC预后相关的GRGs，并构建了两个GRGs相关的基因特征来预测HCC的OS和DFS。本研究结果可能有助于预测预后，促进HCC的治疗。在线版本包含补充材料，可在10.1186/s12885-022-09209-9获得。
Hepatocellular carcinoma (HCC) is the most common primary liver cancer in the world. Although great advances in HCC diagnosis and treatment have been achieved, due to the complicated mechanisms in tumor development and progression, the prognosis of HCC is still dismal. Recent studies have revealed that the Warburg effect is related to the development, progression and treatment of various cancers; however, there have been a few explorations of the relationship between glycolysis and HCC prognosis. mRNA expression profiling was downloaded from public databases. Gene set enrichment analysis (GSEA) was used to explore glycolysis-related genes (GRGs), and the LASSO method and Cox regression analysis were used to identify GRGs related to HCC prognosis and to construct predictive models associated with overall survival (OS) and disease-free survival (DFS). The relationship between the predictive model and the tumor mutation burden (TMB) and tumor immune microenvironment (TIME) was explored. Finally, real-time PCR was used to validate the expression levels of the GRGs in clinical samples and different cell lines. Five GRGs (ABCB6, ANKZF1, B3GAT3, KIF20A and STC2) were identified and used to construct gene signatures to predict HCC OS and DFS. Using the median value, HCC patients were divided into low- and high-risk groups. Patients in the high-risk group had worse OS/DFS than those in the low-risk group, were related to higher TMB and were associated with a higher rate of CD4+ memory T cells resting and CD4+ memory T cells activated. Finally, real-time PCR suggested that the five GRGs were all dysregulated in HCC samples compared to adjacent normal samples. We identified five GRGs associated with HCC prognosis and constructed two GRGs-related gene signatures to predict HCC OS and DFS. The findings in this study may contribute to the prediction of prognosis and promote HCC treatment. The online version contains supplementary material available at 10.1186/s12885-022-09209-9.
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影响因子：
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