Identification of potential biomarkers for diagnosis of pancreatic and biliary tract cancers by sequencing of serum microRNAs

Chanyang Kim,Si Young Song,Kyong Joo Lee,Dawoon E. Jung,Hee Seung Lee,Kwondo Kim,DongAhn Yoo,Jung Hyun Jo,Soo Been Park

doi:10.1186/s12920-019-0521-8

Abstract

BackgroundPancreatic and biliary tract cancer (PC and BTC, respectively) are difficult to diagnose because of their clinical characteristics; however, recent studies suggest that serum microRNAs (miRNAs) might be the key to developing more efficient diagnostic methods for these cancers.MethodsWe analysed the genome-wide expression of serum miRNAs in PC and BTC patients to identify novel biomarker candidates using high-throughput sequencing and experimentally validated miRNAs on clinical samples.ResultsStatistical and classification analysis of the serum miRNA-expression profiles of 55 patient samples showed distinguishable patterns between cancer patients and healthy controls; however, we were unable to distinguish the two cancers. We found that three of the highest performing miRNAs were capable of distinguishing cancer patients from controls, with an accuracy of 92.7%. Additionally, dysregulation of these three cancer-specific miRNAs was demonstrated in an independent sample group by quantitative reverse transcription polymerase chain reaction.ConclusionsThese results suggested three candidate serum miRNAs (mir-744-5p, mir-409-3p, and mir-128-3p) as potential biomarkers for PC and BTC diagnosis.

Highlights

Pancreatic and biliary tract cancer (PC and BTC, respectively) are difficult to diagnose because of their clinical characteristics; recent studies suggest that serum microRNAs might be the key to developing more efficient diagnostic methods for these cancers
principal component analysis (PCA) of the 42 differentially expressed miRNAs separated most of the cancer patients from the healthy control (HC); distribution of pancreatic cancer (PC) and BTC samples remained nearly identical
The result of PCA demonstrated that the differentially expressed miRNAs were effective for distinguishing cancer patients from HCs but were ineffective at distinguishing between the two cancers (Additional file 1: Figure S2)

Summary

Introduction

Pancreatic and biliary tract cancer (PC and BTC, respectively) are difficult to diagnose because of their clinical characteristics; recent studies suggest that serum microRNAs (miRNAs) might be the key to developing more efficient diagnostic methods for these cancers. The high fatality rate has triggered extensive research on these cancers; there has not been remarkable progress in PC and BTC diagnosis. To overcome limitations associated with current diagnostic methods, studies have focused on the development of reliable biomarkers [8,9,10,11], including noncoding RNAs, such as microRNA (miRNA), which are typically 22 nucleotides long and capable of binding to specific recognition sites on mRNAs. By silencing or reducing the expression of ~ 60% of genes in the human genome [12], miRNAs alter the activities of tumour suppressors or key regulators associated with cancer [13]. The detailed function of serum miRNAs is even less-understood than other miRNAs, numerous studies predict that these miRNAs represent an efficient biomarker for the diagnosis of cancers [20,21,22]

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