J Cancer 2014; 5(8):696-705. doi:10.7150/jca.10094

Research Paper

Circulating microRNAs in Pancreatic Juice as Candidate Biomarkers of Pancreatic Cancer

Jin Wang1*, Massimo Raimondo2*, Sushovan Guha3*, Jinyun Chen4, Lixia Diao5, Xiaoqun Dong6, Michael B. Wallace2, Ann M. Killary1,7, Marsha L. Frazier4,7, Timothy A. Woodward2, Jing Wang5, Subrata Sen1,7 ✉

1. Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas;
2. Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida; The University of Texas Medical School and Health Science Center at Houston, Texas;
3. Division of Gastroenterology, Hepatology, and Nutrition, The University of Texas Medical School and Health Science Center at Houston, Texas;
4. Epidemiology, Bioinformatics and Computational Biology, UT MD Anderson Cancer Center, Houston Texas;
5. Bioinformatics and Computational Biology, UT MD Anderson Cancer Center, Houston Texas;
6. Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, The University of Rhode Island, Kingston, Rhode Island;
7. Program in Human and Molecular Genetics, The University of Texas Graduate school of Biomedical Sciences, Houston, Texas.
* These authors contributed equally to this work.

Abstract

Development of sensitive and specific biomarkers, preferably those circulating in body fluids is critical for early diagnosis of cancer. This study performed profiling of microRNAs (miRNAs) in exocrine pancreatic secretions (pancreatic juice) by microarray analysis utilizing pancreatic juice from 6 pancreatic ductal adenocarcinoma (PDAC) patients and two pooled samples from 6 non-pancreatic, non-healthy (NPNH) as controls. Differentially circulating miRNAs were subsequently validated in 88 pancreatic juice samples from 50 PDAC, 19 chronic pancreatitis (CP) patients and 19 NPNH controls. A marked difference in the profiles of four circulating miRNAs (miR-205, miR-210, miR-492, and miR-1427) was observed in pancreatic juice collected from patients with PDAC and those without pancreatic disease. Elevated levels of the four miRNAs together predicted PDAC with a specificity of 88% and sensitivity of 87%. Inclusion of serum CA19-9 level increased the sensitivity to 91% and the specificity to 100%. Enrichment of the four miRNAs in pancreatic juice was associated with decreased OS, as was the combination of miR-205 and miR-210. Higher contents of miR-205 and miR-210 were also associated with lymph node metastasis. Elevated levels of circulating miR-205, miR-210, miR-492, and miR-1247 in pancreatic juice are, therefore, promising candidate biomarkers of disease and poor prognosis in patients with PDAC.

Keywords: miRNA, circulating, biomarker, pancreatic juice, pancreatic cancer.

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How to cite this article:
Wang J, Raimondo M, Guha S, Chen J, Diao L, Dong X, Wallace MB, Killary AM, Frazier ML, Woodward TA, Wang J, Sen S. Circulating microRNAs in Pancreatic Juice as Candidate Biomarkers of Pancreatic Cancer. J Cancer 2014; 5(8):696-705. doi:10.7150/jca.10094. Available from http://www.jcancer.org/v05p0696.htm