Department of Medical Genetics, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
PLoS One. 2012;7(2):e31587. doi: 10.1371/journal.pone.0031587. Epub 2012 Feb 13.
Colorectal cancer (CRC) is one of the leading malignant cancers with a rapid increase in incidence and mortality. The recurrences of CRC after curative resection are sometimes unavoidable and often take place within the first year after surgery. MicroRNAs may serve as biomarkers to predict early recurrence of CRC, but identifying them from over 1,400 known human microRNAs is challenging and costly. An alternative approach is to analyze existing expression data of messenger RNAs (mRNAs) because generally speaking the expression levels of microRNAs and their target mRNAs are inversely correlated. In this study, we extracted six mRNA expression data of CRC in four studies (GSE12032, GSE17538, GSE4526 and GSE17181) from the gene expression omnibus (GEO). We inferred microRNA expression profiles and performed computational analysis to identify microRNAs associated with CRC recurrence using the IMRE method based on the MicroCosm database that includes 568,071 microRNA-target connections between 711 microRNAs and 20,884 gene targets. Two microRNAs, miR-29a and miR-29c, were disclosed and further meta-analysis of the six mRNA expression datasets showed that these two microRNAs were highly significant based on the Fisher p-value combination (p = 9.14 × 10(-9) for miR-29a and p = 1.14 × 10(-6) for miR-29c). Furthermore, these two microRNAs were experimentally tested in 78 human CRC samples to validate their effect on early recurrence. Our empirical results showed that the two microRNAs were significantly down-regulated (p = 0.007 for miR-29a and p = 0.007 for miR-29c) in the early-recurrence patients. This study shows the feasibility of using mRNA profiles to indicate microRNAs. We also shows miR-29a/c could be potential biomarkers for CRC early recurrence.
结直肠癌（CRC）是发病率和死亡率迅速上升的主要恶性肿瘤之一。CRC 根治性切除术后的复发有时是不可避免的，并且通常发生在手术后的第一年。微小 RNA （miRNA）可能作为预测 CRC 早期复发的生物标志物，但从 1400 多种已知的人类 miRNA 中识别它们是具有挑战性和昂贵的。一种替代方法是分析信使 RNA （mRNA）的现有表达数据，因为通常来说，miRNA 和其靶 mRNA 的表达水平呈负相关。在这项研究中，我们从基因表达综合数据库（GEO）中提取了四项研究（GSE12032、GSE17538、GSE4526 和 GSE17181）中六个结直肠癌的 mRNA 表达数据。我们推断 miRNA 表达谱，并使用基于包含 711 个 miRNA 和 20884 个基因靶标的 MicroCosm 数据库的 IMRE 方法进行计算分析，以识别与 CRC 复发相关的 miRNA。两个 miRNA ，miR-29a 和 miR-29c 被揭示出来，并且对六个 mRNA 表达数据集的进一步荟萃分析表明，这两个 miRNA 根据 Fisher p 值组合具有高度显著性（miR-29a 的 p = 9.14 × 10（-9），miR-29c 的 p = 1.14 × 10（-6））。此外，在 78 个人 CRC 样本中对这两个 miRNA 进行了实验验证，以验证它们对早期复发的影响。我们的实验结果表明，这两个 miRNA 在早期复发患者中显著下调（miR-29a 的 p = 0.007，miR-29c 的 p = 0.007）。这项研究表明，使用 mRNA 谱来指示 miRNA 的可行性。我们还表明，miR-29a/c 可能是 CRC 早期复发的潜在生物标志物。
