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miR-133a-3p 作为肝细胞癌诊断指标的效用:一项结合 GEO、TCGA、荟萃分析和生物信息学的研究。

Utility of miR‑133a‑3p as a diagnostic indicator for hepatocellular carcinoma: An investigation combined with GEO, TCGA, meta‑analysis and bioinformatics.

机构信息

Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, Zhuang Autonomous Region 530021, P.R. China.

Department of Medical Ultrasonics, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, Zhuang Autonomous Region 530021, P.R. China.

出版信息

Mol Med Rep. 2018 Jan;17(1):1469-1484. doi: 10.3892/mmr.2017.8040. Epub 2017 Nov 14.

DOI:10.3892/mmr.2017.8040
PMID:29138825
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5780086/
Abstract

Increasing evidence has demonstrated that microRNA (miR)‑133a‑3p is an important regulator of hepatocellular carcinoma (HCC). In the present study, the diagnostic role of miR‑133a‑3p in HCC, and the potential functional pathways, were both explored based on publicly available data. Eligible microarray datasets were collected from NCBI Gene Expression Omnibus (GEO) database and ArrayExpress database. The data related to HCC and matched adjacent normal tissues were also downloaded from The Cancer Genome Atlas (TCGA). Published studies reporting the association between miR‑133a‑3p expression and HCC were reviewed from multiple databases. By combining the data derived from three sources (GEO, TCGA and published studies), the authors analyzed the comprehensive relationship between miR‑133a‑3p expression and clinicopathological features of HCC. Eventually, putative targets of miR‑133a‑3p in HCC were selected for further bioinformatics prediction. A total of eight published microarray datasets were gathered, and the pooled results demonstrated that the expression of miR‑133a‑3p in the tumor group was lower than that in normal groups [standardized mean difference (SMD)=‑0.54; 95% confidence interval (CI), ‑0.74 to ‑0.35; P<0.001]. Consistently, the level of miR‑133a‑1 in HCC was reduced markedly compared to normal tissues (P<0.001) based on TCGA data, and the AUC value of low miR‑133a‑1 expression for HCC diagnosis was 0.670 (P<0.001). Furthermore, the combined SMD of all datasets (GEO, TCGA and literature) suggested that significant difference was observed between the HCC group and the normal control group, and lower miR‑133a‑3p expression in HCC group was noted (SMD=‑0.69; 95% CI, ‑1.10 to ‑0.29; P=0.001). In addition, the authors discovered five key genes of the calcium signaling pathway (NOS1, ADRA1A, ADRA1B, ADRA1D and TBXA2R) that may probably be targeted by miR‑133a‑3p in HCC. The study reveals that miR‑133a‑3p may function as a tumor suppressor in HCC. The prospective novel pathways and key genes of miR‑133a‑3p could offer potential biomarkers for HCC; however, the predictions require further confirmation.

摘要

越来越多的证据表明,微小 RNA(miR)-133a-3p 是肝细胞癌(HCC)的重要调控因子。在本研究中,基于公开数据,同时探讨了 miR-133a-3p 在 HCC 中的诊断作用及其潜在的功能途径。从 NCBI Gene Expression Omnibus(GEO)数据库和 ArrayExpress 数据库中收集了符合条件的微阵列数据集。还从癌症基因组图谱(TCGA)下载了与 HCC 相关的匹配癌旁正常组织的数据。从多个数据库中综述了报道 miR-133a-3p 表达与 HCC 之间关联的已发表研究。通过结合来自三个来源(GEO、TCGA 和已发表研究)的数据,作者分析了 miR-133a-3p 表达与 HCC 临床病理特征之间的综合关系。最终,选择 HCC 中 miR-133a-3p 的潜在靶标进行进一步的生物信息学预测。共收集了 8 个已发表的微阵列数据集,合并结果表明,肿瘤组 miR-133a-3p 的表达低于正常组[标准化均数差(SMD)=-0.54;95%置信区间(CI),-0.74 至-0.35;P<0.001]。同样,根据 TCGA 数据,HCC 中的 miR-133a-1 水平明显低于正常组织(P<0.001),低 miR-133a-1 表达用于 HCC 诊断的 AUC 值为 0.670(P<0.001)。此外,所有数据集(GEO、TCGA 和文献)的合并 SMD 表明,HCC 组与正常对照组之间存在显著差异,并且 HCC 组的 miR-133a-3p 表达较低(SMD=-0.69;95%CI,-1.10 至-0.29;P=0.001)。此外,作者发现了五个钙信号通路的关键基因(NOS1、ADRA1A、ADRA1B、ADRA1D 和 TBXA2R),它们可能是 HCC 中 miR-133a-3p 的靶标。该研究表明,miR-133a-3p 可能在 HCC 中作为肿瘤抑制因子发挥作用。miR-133a-3p 的新潜在途径和关键基因可能为 HCC 提供潜在的生物标志物;然而,这些预测需要进一步验证。

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