Background Increasing studies have suggested that aberrant expression of microRNAs might play essential roles in the progression of cancers. In this study, we sought to construct a high-specific and superior microRNAs signature to improve the survival prediction of colon adenocarcinoma (COAD) patients. Methods The genome-wide miRNAs, mRNA and lncRNA expression profiles and corresponding clinical information of COAD were collected from the TCGA database. Differential expression analysis, Kaplan-Meier curve and time-dependent ROC curve were calculated and performed using R software and GraphPad Prism7. Univariate and multivariate Cox analysis was performed to evaluate the prognostic ability of signature. Functional enrichment analysis was analyzed using STRING database. Results We identified ten prognosis-related microRNAs, including seven risky factors (hsa-miR-197, hsa-miR-32, hsa-miR-887, hsa-miR-3199-2, hsa-miR-4999, hsa-miR-561, hsa-miR-210) and three protective factors (hsa-miR-3917, hsa-miR-3189, hsa-miR-6854). The Kaplan-Meier survival analysis showed that the patients with high risk score had shorter overall survival (OS) in test series. And the similar results were observed in both validation and entire series. The time-dependent ROC curve suggested this signature have high accuracy of OS for COAD. The Multivariate Cox regression analysis and stratification analysis suggested that the ten-microRNA signature was an independent factor after being adjusted with other clinical characteristics. In addition, we also found microRNA signature have higher AUC than other signature. Furthermore, we identified some miRNA-target genes that affect lymphatic metastasis and invasion of COAD patients. Conclusion In this study, we established a ten-microRNA signature as a potentially reliable and independent biomarker for survival prediction of COAD patients.

中文翻译：

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将 10 个 microRNA 特征鉴定为结肠腺癌的优良预后生物标志物。

背景 越来越多的研究表明，microRNA 的异常表达可能在癌症进展中发挥重要作用。在这项研究中，我们试图构建一个高特异性和优越的 microRNA 特征，以提高结肠腺癌 (COAD) 患者的生存预测。方法从TCGA数据库收集COAD的全基因组miRNA、mRNA和lncRNA表达谱及相应的临床信息。使用R软件和GraphPad Prism7计算并执行差异表达分析、Kaplan-Meier曲线和时间依赖性ROC曲线。进行单变量和多变量 Cox 分析以评估特征的预后能力。使用STRING数据库分析功能富集分析。结果 我们确定了十个与预后相关的 microRNA，包括七个危险因素（hsa-miR-197、hsa-miR-32、hsa-miR-887、hsa-miR-3199-2、hsa-miR-4999、hsa-miR-561、hsa-miR-210）和三种保护因子（hsa-miR-3917、hsa-miR-3189、hsa-miR-6854）。Kaplan-Meier 生存分析显示，高风险评分的患者在测试系列中的总生存期 (OS) 较短。在验证和整个系列中都观察到了类似的结果。时间相关的 ROC 曲线表明该特征对 COAD 的 OS 具有较高的准确性。多变量 Cox 回归分析和分层分析表明，在与其他临床特征进行调整后，十个 microRNA 特征是一个独立因素。此外，我们还发现 microRNA 签名比其他签名具有更高的 AUC。此外，我们确定了一些影响 COAD 患者淋巴转移和侵袭的 miRNA 靶基因。结论 在这项研究中，我们建立了一个 10 个 microRNA 特征，作为 COAD 患者生存预测的潜在可靠和独立的生物标志物。