LINC01767 在肝细胞癌中的诊断和预后作用。

IF 2.5 Q2 GASTROENTEROLOGY & HEPATOLOGY World Journal of Hepatology Pub Date : 2024-06-27 DOI:10.4254/wjh.v16.i6.932
Li Zhang, Tong-Xing Cui, Xiang-Zhi Li, Chong Liu, Wen-Qin Wang
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引用次数: 0

摘要

背景:在全球范围内,肝细胞癌(HCC)是导致癌症相关死亡率的主要因素。然而,人们对其潜在的分子机制仍然知之甚少。长非编码 RNA 是新出现的 HCC 诊断、预后和治疗靶标。目的:进行多组学分析,首次探索 LINC01767 在 HCC 中的作用:方法:使用DESeq2软件包分析不同基因的表达。受体操作特征曲线评估了诊断性能。采用Kaplan-Meier单变量分析和Cox多变量分析进行生存分析。最小绝对收缩和选择算子(LASSO)-Cox用于确定预测模型。通过定量实时聚合酶链反应验证了LINC01767在HCC新鲜冰冻组织中的表达,随后进行了LINC01767过度表达的新一代测序(GSE243371),并进行了基因本体/京都基因和基因组百科全书/基因组富集分析/ingenuity通路分析。在 Huh7 细胞中进行了体外实验:结果:LINC01767在HCC中下调,对折变化=1.575,与癌症干性呈正相关。LINC01767 是一个很好的诊断标志物,其曲线下面积(AUC)为[0.801,95% 置信区间(CI):0.751-0.852,P = 0.0106],并且是总生存率(OS)的独立预测因子,其危险比为 1.899(95%CI:1.01-3.58,P = 0.048)。LINC01767提名图模型的表现令人满意。LINC01767的顶级调控网络分析显示了参与各种通路的基因的调控。LASSO回归发现,在预测OS方面,9基因模型的AUC>0.75,比5基因模型的AUC>0.75表现更佳。LINC01767在肿瘤组织和癌细胞系中的表达明显低于瘤旁组织;LINC01767的过度表达抑制了体外Huh7的细胞增殖和克隆形成:结论:LINC01767是HCC中一个重要的抑癌基因,具有良好的诊断和预后作用。
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Diagnostic and prognostic role of LINC01767 in hepatocellular carcinoma.

Background: Hepatocellular carcinoma (HCC) is a primary contributor to cancer-related mortality on a global scale. However, the underlying molecular mechanisms are still poorly understood. Long noncoding RNAs are emerging markers for HCC diagnosis, prognosis, and therapeutic target. No study of LINC01767 in HCC was published.

Aim: To conduct a multi-omics analysis to explore the roles of LINC01767 in HCC for the first time.

Methods: DESeq2 Package was used to analyze different gene expressions. Receiver operating characteristic curves assessed the diagnostic performance. Kaplan-Meier univariate and Cox multivariate analyses were used to perform survival analysis. The least absolute shrinkage and selection operator (LASSO)-Cox was used to identify the prediction model. Subsequent to the validation of LINC01767 expression in HCC fresh frozen tissues through quantitative real time polymerase chain reaction, next generation sequencing was performed following LINC01767 over expression (GSE243371), and Gene Ontology/Kyoto Encyclopedia of Genes and Genomes/Gene Set Enrichment Analysis/ingenuity pathway analysis was carried out. In vitro experiment in Huh7 cell was carried out.

Results: LINC01767 was down-regulated in HCC with a log fold change = 1.575 and was positively correlated with the cancer stemness. LINC01767 was a good diagnostic marker with area under the curve (AUC) [0.801, 95% confidence interval (CI): 0.751-0.852, P = 0.0106] and an independent predictor for overall survival (OS) with hazard ratio = 1.899 (95%CI: 1.01-3.58, P = 0.048). LINC01767 nomogram model showed a satisfied performance. The top-ranked regulatory network analysis of LINC01767 showed the regulation of genes participating various pathways. LASSO regression identified the 9-genes model showing a more satisfied performance than 5-genes model to predict the OS with AUC > 0.75. LINC01767 was down-expressed obviously in tumor than para-tumor tissues in our cohort as well as in cancer cell line; the over expression of LINC01767 inhibit cell proliferation and clone formation of Huh7 in vitro.

Conclusion: LINC01767 was an important tumor suppressor gene in HCC with good diagnostic and prognostic performance.

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来源期刊
World Journal of Hepatology
World Journal of Hepatology GASTROENTEROLOGY & HEPATOLOGY-
CiteScore
4.10
自引率
4.20%
发文量
172
期刊最新文献
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