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长链非编码 RNA ROR1-AS1 高表达及其在肝癌中的预后意义。

LncRNA ROR1‑AS1 high expression and its prognostic significance in liver cancer.

机构信息

Department of Hepatobiliary‑Pancreatic Surgery, China‑Japan Union Hospital of Jilin University, Changchun, Jilin 130000, P.R. China.

Department of General Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.

出版信息

Oncol Rep. 2020 Jan;43(1):55-74. doi: 10.3892/or.2019.7398. Epub 2019 Nov 4.

Abstract

Hepatocellular carcinoma (HCC) is a common disease of the digestive system with no curative treatments. Long noncoding RNA tyrosine protein kinase transmembrane receptor 1 antisense RNA 1 (lncRNA ROR1‑AS1) is an lncRNA whose functions have been predicted in human diseases; however, its important role in cancer has been probed only in mantle cell lymphoma, not in HCC. Therefore, the present study aimed to elucidate the prognostic significance of lncRNA ROR1‑AS1 in HCC. The Cancer Genome Atlas Liver Hepatocellular Carcinoma was used to analyze the expression of ROR1‑AS1 in liver cancer. χ2 tests were performed to evaluate associations between clinical characteristics and ROR1‑AS1 expression. The role of ROR1‑AS1 in HCC prognosis was assessed using Kaplan‑Meier curves and proportional hazards model (Cox) analysis. Gene set enrichment analysis was performed by using a Gene Expression Omnibus dataset. At the same time, Multi Experiment Matrix was used to predict genes that may be co‑expressed with ROR1‑AS1. The Database for Annotation, Visualization and Integrated Discovery and KO‑Based Annotation System were used to analyze the most closely associated cytological behaviors and pathways in HCC. Then, the genes in the three databases were integrated to screen mRNAs, microRNAs and lncRNAs that had co‑expression relationships with ROR1‑AS1. Cytoscape, Search Tool for the Retrieval of Interacting Genes/Proteins and Molecular Evolutionary Genetics Analysis were used to map potential regulatory networks and developmental relationships associated with ROR1‑AS1. Finally, 12 genes most closely associated with ROR1‑AS1 were identified, and their relationship was described using a Circos plot. The results showed that ROR1‑AS1 was upregulated in HCC, and its expression was related to clinical stage, T stage and N stage. Furthermore, Kaplan‑Meier curves and Cox analysis indicated that high expression of ROR1‑AS1 was associated with poor prognosis, and that ROR1‑AS1 was an independent risk factor for HCC. Co‑expression data suggested that there may be a large regulatory network of 45 genes with indirect associations with ROR1‑AS1, a small regulatory network of 15 genes with direct or indirect regulatory relationships, and a special regulatory network containing 12 genes directly associated with ROR1‑AS1. The present findings indicated that high expression of ROR1‑AS1 suggests poor prognosis in patients with HCC.

摘要

肝细胞癌(HCC)是一种常见的消化系统疾病,目前尚无治愈方法。长链非编码 RNA 酪氨酸蛋白激酶跨膜受体 1 反义 RNA 1(lncRNA ROR1-AS1)是一种 lncRNA,其在人类疾病中的功能已被预测;然而,其在癌症中的重要作用仅在套细胞淋巴瘤中得到了探究,而在 HCC 中尚未得到探究。因此,本研究旨在阐明 lncRNA ROR1-AS1 在 HCC 中的预后意义。使用癌症基因组图谱肝脏肝癌数据库分析 ROR1-AS1 在肝癌中的表达。χ2 检验用于评估临床特征与 ROR1-AS1 表达之间的关联。使用 Kaplan-Meier 曲线和比例风险模型(Cox)分析评估 ROR1-AS1 对 HCC 预后的作用。通过使用基因表达综合数据集进行基因集富集分析。同时,使用多实验矩阵预测可能与 ROR1-AS1 共表达的基因。使用数据库注释、可视化和综合发现以及基于 KO 的注释系统分析 HCC 中最密切相关的细胞学行为和途径。然后,整合三个数据库中的基因,筛选与 ROR1-AS1 共表达的 mRNAs、microRNAs 和 lncRNAs。使用 Cytoscape、搜索工具检索相互作用基因/蛋白质和分子进化遗传学分析来映射与 ROR1-AS1 相关的潜在调控网络和发育关系。最后,确定了与 ROR1-AS1 最密切相关的 12 个基因,并使用 Circos 图描述它们之间的关系。结果显示,ROR1-AS1 在 HCC 中上调,其表达与临床分期、T 分期和 N 分期相关。此外,Kaplan-Meier 曲线和 Cox 分析表明,ROR1-AS1 高表达与预后不良相关,且 ROR1-AS1 是 HCC 的独立危险因素。共表达数据表明,可能存在一个包含 45 个与 ROR1-AS1 间接相关的基因的大调控网络、一个包含 15 个具有直接或间接调控关系的基因的小调控网络,以及一个包含 12 个与 ROR1-AS1 直接相关的基因的特殊调控网络。本研究结果表明,ROR1-AS1 高表达提示 HCC 患者预后不良。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6906/6908930/2707c0a3876e/or-43-01-0055-g00.jpg

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