Department of Clinical Laboratory, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.
Department of Hepatobiliary Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.
Life Sci. 2019 Sep 1;232:116596. doi: 10.1016/j.lfs.2019.116596. Epub 2019 Jun 22.
The aim of the study was to identify key miRNAs related to hepatocellular carcinoma (HCC) and then to explore their potential function and clinical significance.
The miRNA expression profiles of 387 HCC and 62 normal liver tissues were obtained from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. GEO2R tool and edgeR package in R/Bioconductor were used to screen out HCC-related miRNAs. VennDiagram package was used to identify key miRNAs related to HCC. The miRWalk tool and multiple R packages, such as pROC and survival, were used to explore potential function and clinical significance of these key miRNAs.
A total of 17 and 300 HCC-related human miRNAs were identified in GEO dataset and TCGA, respectively. Thereinto seven miRNAs including hsa-miR-199a-3p, hsa-miR-199b-3p, hsa-miR-139-5p, hsa-miR-139-3p, hsa-miR-424-3p, hsa-miR-1269b and hsa-miR-1269a were key miRNAs related to HCC. Functional enrichment analysis showed that these key miRNAs were involved in multiple biological processes, such as telomere maintenance via telomerase, protein sumoylation, histone mRNA metabolic process and angiotensin maturation. Cox regression analysis indicated that hsa-miR-139-5p expression was associated with the prognosis of HCC patients. ROC curve analysis suggested that survival prediction model developed based on tumor stage and hsa-miR-139-5p exhibited good performance in predicting 3-year overall survival of HCC patients.
The present study identified several HCC-related miRNAs, which might serve as new diagnostic markers and therapeutic targets for HCC. In addition, hsa-miR-139-5p might act as a promising prognostic indicator for HCC patients.
本研究旨在鉴定与肝细胞癌（HCC）相关的关键 miRNA，并探讨其潜在功能和临床意义。
从基因表达综合数据库（GEO）和癌症基因组图谱（TCGA）数据库中获取了 387 例 HCC 和 62 例正常肝组织的 miRNA 表达谱。使用 GEO2R 工具和 R/Bioconductor 中的 edgeR 包筛选出与 HCC 相关的 miRNA。使用 VennDiagram 包鉴定与 HCC 相关的关键 miRNA。使用 miRWalk 工具和多个 R 包，如 pROC 和 survival，探索这些关键 miRNA的潜在功能和临床意义。
在 GEO 数据集和 TCGA 中分别鉴定出 17 个和 300 个与 HCC 相关的人类 miRNA。其中，hsa-miR-199a-3p、hsa-miR-199b-3p、hsa-miR-139-5p、hsa-miR-139-3p、hsa-miR-424-3p、hsa-miR-1269b 和 hsa-miR-1269a 等 7 个 miRNA 是与 HCC 相关的关键 miRNA。功能富集分析表明，这些关键 miRNA参与了多个生物学过程，如通过端粒酶维持端粒、蛋白质 SUMO 化、组蛋白 mRNA 代谢过程和血管紧张素成熟。Cox 回归分析表明，hsa-miR-139-5p 的表达与 HCC 患者的预后相关。ROC 曲线分析表明，基于肿瘤分期和 hsa-miR-139-5p 构建的生存预测模型在预测 HCC 患者 3 年总生存率方面表现出良好的性能。
本研究鉴定了一些与 HCC 相关的 miRNA，它们可能成为 HCC 的新诊断标志物和治疗靶点。此外，hsa-miR-139-5p 可能是 HCC 患者有前途的预后指标。
