缺氧相关长链非编码RNA作为肝癌预后预测标志物的潜在价值
收稿日期: 2021-12-02
修回日期: 2022-01-11
网络出版日期: 2022-01-19
基金资助
国家重点研发计划编号(2017YFA0504301);国家自然科学基金重大研究计划重点项目资助编号(91440206)
Prognostic and predictive value of the hypoxia-associated long non-coding RNA signature in hepatocellular carcinoma
Received date: 2021-12-02
Revised date: 2022-01-11
Online published: 2022-01-19
Supported by
Supported by the National Key Research and Development Program of China No(2017YFA0504301);the Major Research Plan of the National Natural Science Foundation of China No(91440206)
肝细胞癌(hepatocellular carcinoma, 简称肝癌)是一种常见的恶性肿瘤。缺氧是肝癌等实体肿瘤的一个重要特征,同时也是诱导肿瘤恶性进展的重要因素。然而,肝癌缺氧相关的长链非编码RNA(long non-coding RNA,lncRNA)的鉴定及其在临床生存预后等方面的价值仍未得到系统的研究。本研究旨在通过肝癌转录组的整合分析鉴定肝癌缺氧相关的lncRNA,并评估其在肝癌预后中的价值。基于癌症基因组图谱(The Cancer Genome Atlas, TCGA)计划的肝癌转录组数据的整合分析,初步鉴定到233个缺氧相关的候选lncRNA。进一步筛选具有预后价值的候选者,基于其中12个缺氧相关lncRNA (AC012676.1、PRR7-AS1、AC020915.2、AC008622.2、AC026401.3、MAPKAPK5-AS1、MYG1-AS1、AC015908.3、AC009275.1、MIR210HG、CYTOR和SNHG3)建立了肝癌预后风险模型。Cox比例风险回归分析显示,基于该模型计算的缺氧风险评分作为肝癌患者新的独立预后预测指标,优于传统的临床病理因素。基因集富集分析显示,缺氧风险评分反映了细胞增殖相关通路的活化和脂代谢过程的失活。综上所述,本研究构建了一个基于缺氧相关lncRNA的风险评分模型,可以作为肝癌患者预后预测的候选指标,并初步提示了这些缺氧相关的lncRNA在肝癌防治中的重要作用。
程敏, 张静, 曹鹏博, 周钢桥 . 缺氧相关长链非编码RNA作为肝癌预后预测标志物的潜在价值[J]. 遗传, 2022 , 44(2) : 153 -167 . DOI: 10.16288/j.yczz.21-416
Hepatocellular carcinoma (HCC) is a common cancer worldwide. Hypoxia is an important feature of solid tumors, including HCC, and is also an important factor involved in malignancy progression. However, the identification of hypoxia-related long non-coding RNA (lncRNAs) and their prognostic value in HCC have not been systematically investigated. The aim of this study is to identify the features based on the hypoxia-related lncRNAs and evaluate their predictive value for HCC prognosis. Based on the integrated analysis of HCC transcriptome data from The Cancer Genome Atlas (TCGA), we had identified 233 potential hypoxia-related lncRNAs. We further evaluated the prognostic value of these lncRNAs and optimally established a 12-lncRNA (AC012676.1, PRR7-AS1, AC020915.2, AC008622.2, AC026401.3, MAPKAPK5-AS1, MYG1-AS1, AC015908.3, AC009275.1, MIR210HG, CYTOR and SNHG3) prognostic risk model. The Cox proportional hazards regression analysis revealed that the hypoxia risk score is a novel independent prognostic predictor for HCC patients, which outperforms the traditional clinical pathological factors. Gene set enrichment analysis (GSEA) showed that the hypoxia risk score reflects the activation of biological features related to cell proliferation and the inactivation of lipid metabolism processes. In summary, we had constructed a risk score model based on 12 hypoxia-related lncRNAs, which might be a promising prognostic predictor for HCC patients and highlight their potential roles in the prevention and treatment of this malignancy.
Key words： hepatocellular carcinoma; hypoxia; long non-coding RNA; prognostic model
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