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胰腺癌中预后微小 RNA 及其潜在的分子机制:基于癌症基因组图谱和生物信息学研究的一项研究。

Prognostic microRNAs and their potential molecular mechanism in pancreatic cancer: A study based on The Cancer Genome Atlas and bioinformatics investigation.

机构信息

Department of General Surgery, Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region 530021, P.R. China.

Department of Pathology, 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):939-951. doi: 10.3892/mmr.2017.7945. Epub 2017 Nov 3.

Abstract

Although certain biomarkers that are directly associated with the overall survival (OS) of patients with pancreatic adenocarcinoma (PAAD) have been identified, the efficacy of a single factor is limited to predicting the prognosis. The aim of the present study was to identify a combination micro (mi)RNA signature that enhanced the prognostic prediction for PAAD. Following analysis of the data available from The Cancer Genome Atlas (TCGA), 175 PAAD samples were selected for the present study, and the associations between 494 miRNAs and OS were investigated. The prognostic value of all miRNAs was analyzed by multivariate Cox regression, and the miRNAs were ranked according to the hazard ratio (HR) and P‑values. The top 5 miRNAs (miR‑1301, miR‑125a, miR‑376c, miR‑328 and miR‑376b) were significantly associated with OS (HR=0.139; 95% confidence interval, 0.043‑0.443; P<0.001), thus demonstrating that this panel was able to serve as an independent prognostic factor for PAAD. In addition, the present study also predicted the target genes of the top 10 miRNAs with the highest prognostic values using 12 different prediction software, and enrichment signaling pathway analyses elucidated that several pathways may be markedly associated with these miRNAs, including 'Pathways in cancer', 'Chronic myeloid leukemia', 'Glioma' and 'MicroRNAs in cancer'. Lastly, ubiquitin C, epidermal growth factor receptor, estrogen receptor 1, mitogen‑activated protein kinase 1, mothers against decapentaplegic homolog 4 and androgen receptor may be the hub genes revealed by STRING analysis. The present study identified several miRNAs, particularly a five‑miRNA‑pool, that may be reliable, independent factors for predicting survival in patients with PAAD. However, the underlying molecular mechanisms require further investigation in the future.

摘要

虽然已经确定了与胰腺导管腺癌 (PAAD) 患者总生存期 (OS) 直接相关的某些生物标志物,但单个因素的疗效仅限于预测预后。本研究旨在确定增强 PAAD 预后预测的组合微 (mi)RNA 特征。在分析了来自癌症基因组图谱 (TCGA) 的可用数据后,本研究选择了 175 个 PAAD 样本,并研究了 494 个 miRNA 与 OS 的关联。通过多变量 Cox 回归分析了所有 miRNA 的预后价值,并根据风险比 (HR) 和 P 值对 miRNA 进行了排序。前 5 个 miRNA (miR-1301、miR-125a、miR-376c、miR-328 和 miR-376b) 与 OS 显著相关 (HR=0.139;95%置信区间,0.043-0.443;P<0.001),表明该模型能够作为 PAAD 的独立预后因素。此外,本研究还使用 12 种不同的预测软件预测了前 10 个具有最高预后价值的 miRNA 的靶基因,富集信号通路分析表明,几种途径可能与这些 miRNA 明显相关,包括“癌症途径”、“慢性髓系白血病”、“神经胶质瘤”和“癌症中的 microRNAs”。最后,通过 STRING 分析发现,泛素 C、表皮生长因子受体、雌激素受体 1、丝裂原活化蛋白激酶 1、母性对抗 decapentaplegic 同源物 4 和雄激素受体可能是 STRING 分析揭示的枢纽基因。本研究确定了几种 miRNA,特别是五 miRNA 池,可能是预测 PAAD 患者生存的可靠、独立因素。然而,潜在的分子机制需要在未来进一步研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb96/5780175/93ae28172178/MMR-17-01-0939-g00.jpg

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