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LINC01767在肝细胞癌中的诊断和预后作用。

Diagnostic and prognostic role of LINC01767 in hepatocellular carcinoma.

作者信息

Zhang Li, Cui Tong-Xing, Li Xiang-Zhi, Liu Chong, Wang Wen-Qin

机构信息

Department of Thyroid and Breast Surgery, The Affiliated People Hospital of Second Medical University, Weifang 266010, Shandong Province, China.

Department of General Surgery, Qingdao Municipal Hospital Group, Qingdao 266237, Shandong Province, China.

出版信息

World J Hepatol. 2024 Jun 27;16(6):932-950. doi: 10.4254/wjh.v16.i6.932.

Abstract

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. 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, = 0.0106] and an independent predictor for overall survival (OS) with hazard ratio = 1.899 (95%CI: 1.01-3.58, = 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 .

CONCLUSION

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

摘要

背景

肝细胞癌(HCC)是全球癌症相关死亡的主要原因。然而,其潜在的分子机制仍知之甚少。长链非编码RNA正在成为HCC诊断、预后和治疗靶点的新兴标志物。尚未有关于LINC01767在HCC中的研究发表。

目的

首次进行多组学分析以探索LINC01767在HCC中的作用。

方法

使用DESeq2软件包分析不同基因的表达。通过绘制受试者工作特征曲线评估诊断性能。采用Kaplan-Meier单因素分析和Cox多因素分析进行生存分析。使用最小绝对收缩和选择算子(LASSO)-Cox回归识别预测模型。通过定量实时聚合酶链反应验证HCC新鲜冷冻组织中LINC01767的表达后,在LINC01767过表达后进行下一代测序(GSE243371),并进行基因本体论/京都基因与基因组百科全书/基因集富集分析/ Ingenuity通路分析。在Huh7细胞中进行实验。

结果

LINC01767在HCC中表达下调,对数变化倍数=1.575,且与癌症干性呈正相关。LINC01767是一个良好的诊断标志物,曲线下面积(AUC)为[0.801,95%置信区间(CI):0.751-0.852,P=0.0106],是总生存期(OS)的独立预测因子,风险比=1.899(95%CI:1.01-3.58,P=0.048)。LINC01767列线图模型显示出令人满意的性能。对LINC01767的顶级调控网络分析显示其对参与各种途径的基因具有调控作用。LASSO回归确定的9基因模型在预测OS方面比5基因模型表现更令人满意,AUC>0.75。在我们的队列以及癌细胞系中,LINC01767在肿瘤组织中的表达明显低于癌旁组织;LINC01767的过表达抑制了Huh7细胞的增殖和克隆形成。

结论

LINC01767是HCC中一个重要的肿瘤抑制基因,具有良好的诊断和预后性能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4476/11212654/aca6adb596ff/WJH-16-932-g001.jpg

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