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

Journal of Experimental & Clinical Cancer Research

Cheng-Hong Peng¹  Zhi-Wei Quan²  Wei Gong²  Kun Cheng¹  Ming-Zhe Weng²  Xiang Kong³  Ming-Zhe Ma² 

[1] Department of General Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China;Department of General Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, 1665 Kongjiang Road, Shanghai 200092, People’s Republic of China;Department of Pharmacology, Wannan Medical College, Anhui, China

关键词: Biomarker;    Pancreatic cancer;    Meta-analysis;    microRNA;   

Others  :  815094
DOI  :  10.1186/1756-9966-32-71

 received in 2013-05-14, accepted in 2013-09-26,  发布年份 2013

【 摘 要 】

Background

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.

Methods

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.

Results

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.

Conclusions

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.

【 授权许可】

   
2013 Ma et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

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