Circulating miRNA-21-5p as a diagnostic biomarker for pancreatic cancer: evidence from comprehensive miRNA expression profiling analysis and clinical validation

Kai Qu,Hulin Chang,Lei Zhou,Zhixin Wang,Xing Zhang,Ting Lin,Tian Liu,Sushun Liu,Zheng Wu,Jichao Wei,Zheng Wang,Ke Li,Chang Liu

doi:10.1038/s41598-017-01904-z

Abstract

Pancreatic cancer (PC) is a highly fatal disease worldwide and is often misdiagnosed in its early stages. The exploration of novel non-invasive biomarkers will definitely benefit PC patients. Recently, circulating miRNAs in body fluids are emerging as non-invasive biomarkers for PC diagnosis. In this study, we first conducted comprehensive robust rank aggregation (RRA) analysis based on 21 published miRome profiling studies. We statistically identified and clinically validated a miRNA expression pattern in PC patients. These miRNAs consisted of four up-regulated (hsa-miR-21-5p, hsa-miR-31-5p, hsa-miR-210-3p and hsa-miR-155-5p) and three down-regulated miRNAs (hsa-miR-217, hsa-miR-148a-3p and hsa-miR-375). Among them, hsa-miR-21-5p was one of the most highly expressed miRNAs in the serum of PC patients. Our validation test further suggested a relatively high accuracy of serum hsa-miR-21-5p levels in the diagnosis of PC, with a sensitivity of 0.77 and a specificity of 0.80. Finally, a diagnostic meta-analysis based on 9 studies also revealed favorable sensitivity and specificity of circulating hsa-miR-21-5p for the diagnosis of PC (pooled sensitivity and specificity were 0.76 and 0.74, respectively), which was consistent with our findings. Taken together, as one of the most aberrantly expressed miRNAs in PC, circulating hsa-miR-21-5p might be a promising serum biomarker in patients with PC.

Highlights

Pancreatic cancer (PC), which is one of the most common cancers worldwide, is a highly fatal disease with more than 200,000 people diagnosed every year[1]
One hypothesis has clearly demonstrated that cancer cells contribute to the pool of circulating miRNAs, which allows for the detection of cancer-specific miRNAs in a patient’s circulation
We explored miRNA expression patterns in PC based on rank aggregation (RRA) methods and validated the most consistently aberrantly expressed miRNAs in our own cohort

Summary

Introduction

Pancreatic cancer (PC), which is one of the most common cancers worldwide, is a highly fatal disease with more than 200,000 people diagnosed every year[1]. Researchers have put forth great effort to identify tumor-specific miRNAs by high-throughput miRNA profiling techniques, including second-generation sequencing and microarray-based methods[7, 8]. The applications of high-throughput miRNA profiling have enabled researchers to identify a group of differentially expressed miRNAs in cancers, which have potential as biomarkers for diagnostic, prognostic and therapeutic applications[9]. In 2013, Ma et al successfully identified 10 aberrantly expressed miRNAs in PC, which might be potential biomarkers for cancer diagnosis and prognosis[20].

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Results

Conclusion