Meta-analysis of miRNA expression profiles for prostate cancer recurrence following radical prostatectomy.
Meta-analysis of miRNA expression profiles for prostate cancer recurrence following radical prostatectomy.
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DOI：
10.1371/journal.pone.0179543
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Aydin N
中科院分区：
文献类型：
--
作者：
Pashaei E;Pashaei E;Ahmady M;Ozen M;Aydin N
前列腺癌（Prostate cancer，PCa）是目前西方国家男性死亡的主要原因，也是最常见的恶性肿瘤。根治性前列腺切除术（RP）后，近30%的男性发展为临床复发，血清前列腺特异性抗原水平高。PCa研究的一个重要挑战是确定肿瘤复发的有效预测因子。microRNA的分子改变与PCa的发生和进展相关。已经在复发PCa中进行了几项miRNA微阵列研究，但不同研究的结果不同。我们对6个可用的miRNA表达数据集进行了荟萃分析，以确定一组共失调的miRNA基因和重叠的生物学过程。使用“MetaDE”软件包，基于R版本3.3.1中的组合P值方法（自适应权重和Fisher方法）进行荟萃分析。对6个miRNA数据集的荟萃分析显示，miR-125 A、miR-199 A-3 P、miR-28- 5 P、miR-301 B、miR-324- 5 P、miR-361- 5 P、miR-363*、miR-449 A、miR-484、miR-498、miR-579、miR-637、miR-720、miR-874和miR-98是常见的上调的miRNA基因，而miR-1、miR-133 A、miR-133 A、miR-134、miR-134和miR-136是常见的上调的miRNA基因。miR-133 B、miR-137、miR-221、miR-340、miR-370、miR-449 B、miR-489、miR-492、miR-496、miR-541、miR-572、miR-583、miR-606、miR-624、miR-636、miR-639、miR-661、miR-760、miR-890、和miR-939是与非复发性PCa样品相比在复发性PCa样品中通常下调的miRNA基因。基于网络的分析表明，这些miRNA中的一些在其他癌症中具有既定的预后意义，并且可以积极参与肿瘤生长。基因本体富集显示，许多共去调节的miRNA的靶基因参与“上皮细胞增殖的调节”和“组织形态发生”。京都基因和基因组百科全书（KEGG）分析表明这些miRNA调节癌症途径。PPI枢纽蛋白分析鉴定CTNNB 1为最高等级的枢纽蛋白。此外，共同通路分析显示TCF 3、MAX、MYC、CYP 26 A1和SREBF 1与这些DE miRNA基因存在显著的相互作用。已鉴定的基因被称为肿瘤抑制因子和生物标志物，其与几种癌症类型密切相关，例如结肠直肠癌、乳腺癌、PCa、胃癌和肝细胞癌。此外，研究表明，DE miRNA的组合可以帮助更特异地检测PCa和预测生化复发（BCR）。我们发现通过荟萃分析鉴定的miRNAs是根治性前列腺癌切除术后复发的候选预测标志物。
Prostate cancer (PCa) is a leading reason of death in men and the most diagnosed malignancies in the western countries at the present time. After radical prostatectomy (RP), nearly 30% of men develop clinical recurrence with high serum prostate-specific antigen levels. An important challenge in PCa research is to identify effective predictors of tumor recurrence. The molecular alterations in microRNAs are associated with PCa initiation and progression. Several miRNA microarray studies have been conducted in recurrence PCa, but the results vary among different studies. We conducted a meta-analysis of 6 available miRNA expression datasets to identify a panel of co-deregulated miRNA genes and overlapping biological processes. The meta-analysis was performed using the ‘MetaDE’ package, based on combined P-value approaches (adaptive weight and Fisher's methods), in R version 3.3.1. Meta-analysis of six miRNA datasets revealed miR-125A, miR-199A-3P, miR-28-5P, miR-301B, miR-324-5P, miR-361-5P, miR-363*, miR-449A, miR-484, miR-498, miR-579, miR-637, miR-720, miR-874 and miR-98 are commonly upregulated miRNA genes, while miR-1, miR-133A, miR-133B, miR-137, miR-221, miR-340, miR-370, miR-449B, miR-489, miR-492, miR-496, miR-541, miR-572, miR-583, miR-606, miR-624, miR-636, miR-639, miR-661, miR-760, miR-890, and miR-939 are commonly downregulated miRNA genes in recurrent PCa samples in comparison to non-recurrent PCa samples. The network-based analysis showed that some of these miRNAs have an established prognostic significance in other cancers and can be actively involved in tumor growth. Gene ontology enrichment revealed many target genes of co-deregulated miRNAs are involved in “regulation of epithelial cell proliferation” and “tissue morphogenesis”. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated that these miRNAs regulate cancer pathways. The PPI hub proteins analysis identified CTNNB1 as the most highly ranked hub protein. Besides, common pathway analysis showed that TCF3, MAX, MYC, CYP26A1, and SREBF1 significantly interact with those DE miRNA genes. The identified genes have been known as tumor suppressors and biomarkers which are closely related to several cancer types, such as colorectal cancer, breast cancer, PCa, gastric, and hepatocellular carcinomas. Additionally, it was shown that the combination of DE miRNAs can assist in the more specific detection of the PCa and prediction of biochemical recurrence (BCR). We found that the identified miRNAs through meta-analysis are candidate predictive markers for recurrent PCa after radical prostatectomy.