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

ABSTRACT: We profiled expression of serum miRNAs derived from pancreatic and biliary tract cancer patients and detected biomarker candidates using high-throughput sequencing

ORGANISM(S): Homo sapiens

PROVIDER: GSE109319 | GEO | 2019/04/24

REPOSITORIES: GEO

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MicroRNA markers for the diagnosis of pancreatic and biliary tract cancers

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Project description: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.

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Project description:BackgroundCirculating microRNAs (miRNAs), which are extremely stable and protected from RNAse-mediated degradation in body fluids, have emerged as candidate biomarkers for many diseases. The present study aimed to identify a serum microRNA (miRNA) expression profile that could serve as a novel diagnostic biomarker for primary biliary cirrhosis (PBC).MethodsSerum miRNA expression was investigated using four cohorts comprising 380 participants (healthy controls and patients with PBC) recruited between August 2010 and June 2013. miRNA expression was initially analyzed by Illumina sequencing using serum samples pooled from 3 patients and 3 controls. Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) was then used to evaluate the expression of selected miRNAs in a screening set (n?=?40). A logistic regression model was then constructed using a training cohort (n?=?192) and validated using another cohort (n?=?142). The area under the receiver operating characteristic curve (AUC) was used to evaluate diagnostic accuracy.ResultsWe identified a miRNA panel (hsa-miR-122-5p, hsa-miR-141-3p, and hsa-miR-26b-5p) with a high diagnostic accuracy for PBC (AUC?=?0.905, 95% confidence interval (CI)?=?0.857 to 0.953; sensitivity?=?80.5%, specificity?=?88.3%). There was a significant difference between AUC values of the miRNA panel and those of alkaline phosphatase (ALP) (AUC?=?0.537, difference between areas?=?0.314, 95% CI?=?0.195 to 0.434, P<0.001), and those of antinuclear antibody (ANA) (AUC?=?0.739, difference between areas?=?0.112, 95% CI?=?0.012 to 0.213, P?=?0.0282).ConclusionWe identified a serum microRNA panel with considerable clinical value in PBC diagnosis. The results indicate that the miRNA panel is a more sensitive and specific biomarker for PBC than ALP and ANA.

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