Candidate microRNA biomarkers of pancreatic ductal adenocarcinoma: meta-analysis, experimental validation and clinical significance.

Candidate microRNA biomarkers of pancreatic ductal adenocarcinoma: meta-analysis, experimental validation and clinical significance.
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DOI:
10.1186/1756-9966-32-71
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发表时间:
2013-09-28
期刊:
Journal of experimental & clinical cancer research : CR
影响因子:
--
通讯作者:
Peng CH
Peng CH
中科院分区:
其他
文献类型:
--
作者:
Ma MZ;Kong X;Weng MZ;Cheng K;Gong W;Quan ZW;Peng CH

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近年来,microRNA(miRNA)表达异常在胰腺导管腺癌(PDAC)诊断和预后中的价值得到了广泛研究。然而,测量平台和实验室方案的差异以及小样本量可能使基因表达水平无法比拟。对已发表的PDAC研究进行了全面的荟萃审查,比较了PDAC组织和配对的相邻非癌胰腺组织的miRNA表达谱,以确定PDAC的候选miRNA生物标志物。采用了miRNA投票计数策略和最近发表的Robust Rank Aggregation方法。在这篇综述中,共包括538个肿瘤和206个非癌对照样本。我们鉴定了7个上调和3个下调的miRNA的统计学显著的miRNA元签名。实验验证结果表明,miRNA的表达水平与元签名一致。从投票计数策略的结果是一致的,从稳健的秩聚合方法。实验验证证实,通过荟萃审查方法确定的统计学独特特征可以区分PDAC组织与配对的非恶性胰腺组织。在70名患者的队列中,miR-21的高表达(p=0.018,HR=2.610; 95% CI=1.179-5.777)和miR-31(p=0.039,HR=2.735; 95%CI =1.317-6.426),miR-375的低表达(p=0.022,HR=2.337; 95%CI =1.431-5.066)与切除术后不良的总生存率相关,独立于临床协变量。鉴定的miRNA可用于开发一组具有足够灵敏度和特异性的PDAC诊断和预后生物标志物,以用于临床环境。
The diagnostic and prognostic value of microRNA (miRNA) expression aberrations in pancreatic ductal adenocarcinoma (PDAC) has been studied extensively in recent years. However, differences in measurement platforms and lab protocols as well as small sample sizes can render gene expression levels incomparable. A comprehensive meta-review of published studies in PDAC that compared the miRNA expression profiles of PDAC tissues and paired neighbouring noncancerous pancreatic tissues was performed to determine candidate miRNA biomarkers for PDAC. Both a miRNA vote-counting strategy and a recently published Robust Rank Aggregation method were employed. In this review, a total of 538 tumour and 206 noncancerous control samples were included. We identified a statistically significant miRNA meta-signature of seven up- and three down-regulated miRNAs. The experimental validation results showed that the miRNA expression levels were in accordance with the meta-signature. The results from the vote-counting strategy were consistent with those from the Robust Rank Aggregation method. The experimental validation confirmed that the statistically unique profiles identified by the meta-review approach could discriminate PDAC tissues from paired nonmalignant pancreatic tissues. In a cohort of 70 patients, the high expression of miR-21 (p=0.018, HR=2.610; 95% CI=1.179-5.777) and miR-31 (p=0.039, HR=2.735; 95% CI=1.317-6.426), the low expression of miR-375 (p=0.022, HR=2.337; 95% CI=1.431-5.066) were associated with poor overall survival following resection, independent of clinical covariates. The identified miRNAs may be used to develop a panel of diagnostic and prognostic biomarkers for PDAC with sufficient sensitivity and specificity for use in a clinical setting.
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期刊: GENOME RESEARCH
影响因子: 7
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影响因子: 2.7
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