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新型 lncRNA 标志物在人结肠癌肿瘤复发预测中的整合分析。

Integration analysis for novel lncRNA markers predicting tumor recurrence in human colon adenocarcinoma.

机构信息

Department of Epidemiology and Biostatistics, School of Public Health, Xi'an Jiaotong University Health Science Center, 76 Yanta Xilu Road, Xi'an, 710061, Shaanxi, China.

First Affiliated Hospital of Xi'an Jiaotong University, 277 Yanta Xilu Road, Xi'an, 710061, Shaanxi, China.

出版信息

J Transl Med. 2019 Aug 30;17(1):299. doi: 10.1186/s12967-019-2049-2.

Abstract

BACKGROUND

Numerous evidence has suggested that long non-coding RNA (lncRNA) acts an important role in tumor biology. This study focuses on the identification of novel prognostic lncRNA biomarkers predicting tumor recurrence in human colon adenocarcinoma.

METHODS

We obtained the research data from The Cancer Genome Atlas (TCGA) database. The interaction among different expressed lncRNA, miRNA and mRNA markers between colon adenocarcinoma patients with and without tumor recurrence were verified with miRcode, starBase and miRTarBase databases. We established the lncRNA-miRNA-mRNA competing endogenous RNA (ceRNA) network based on the verified association between the selected markers. We performed the functional enrichment analysis to obtain better understanding of the selected lncRNAs. Then we use multivariate logistic regression to identify the prognostic lncRNA markers with covariates. We also generated a nomogram predicting tumor recurrence risk based on the identified lncRNA biomarkers and clinical covariates.

RESULTS

We included 12,727 lncRNA, 1881 miRNA and 47,761 mRNA profiling and clinical features for 113 colon adenocarcinoma patients obtained from the TCGA database. After filtration, we used 37 specific lncRNAs, 60 miRNAs and 148 mRNAs in the ceRNA network analysis. We identified five lncRNAs as prognostic lncRNA markers predicting tumor recurrence in colon adenocarcinoma, in which four of them were identified for the first time. Finally, we generated a nomogram illustrating the association between the identified lncRNAs and the tumor recurrence risk in colon adenocarcinoma.

CONCLUSIONS

The four newly identified lncRNA biomarkers might be potential prognostic biomarkers predicting tumor recurrence in colon adenocarcinoma. We recommend that further clinical and fundamental researches be conducted on the identified lncRNA markers.

摘要

背景

大量证据表明,长链非编码 RNA(lncRNA)在肿瘤生物学中发挥着重要作用。本研究旨在鉴定预测人结肠腺癌肿瘤复发的新型预后 lncRNA 生物标志物。

方法

我们从癌症基因组图谱(TCGA)数据库中获取研究数据。使用 miRcode、starBase 和 miRTarBase 数据库验证了具有肿瘤复发和无肿瘤复发的结肠腺癌患者之间不同表达的 lncRNA、miRNA 和 mRNA 标志物之间的相互作用。我们基于选定标志物之间的验证关联建立了 lncRNA-miRNA-mRNA 竞争内源性 RNA(ceRNA)网络。我们进行了功能富集分析,以更好地理解所选 lncRNAs。然后,我们使用多元逻辑回归来识别具有协变量的预后 lncRNA 标志物。我们还根据鉴定出的 lncRNA 生物标志物和临床协变量生成了预测肿瘤复发风险的列线图。

结果

我们纳入了来自 TCGA 数据库的 113 名结肠腺癌患者的 12727 个 lncRNA、1881 个 miRNA 和 47761 个 mRNA 谱和临床特征。经过筛选,我们在 ceRNA 网络分析中使用了 37 个特异性 lncRNA、60 个 miRNA 和 148 个 mRNA。我们确定了五个 lncRNA 作为预测结肠腺癌肿瘤复发的预后 lncRNA 标志物,其中四个是首次鉴定。最后,我们生成了一个列线图,说明了鉴定出的 lncRNA 与结肠腺癌肿瘤复发风险之间的关系。

结论

这四个新鉴定的 lncRNA 生物标志物可能是预测结肠腺癌肿瘤复发的潜在预后生物标志物。我们建议对鉴定出的 lncRNA 标志物进行进一步的临床和基础研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ad2/6717325/78d5876ab769/12967_2019_2049_Fig2_HTML.jpg

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