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

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.

Pre-operative Plasma miR-21-5p Is a Sensitive Biomarker and Independent Prognostic Factor in Patients with Pancreatic Ductal Adenocarcinoma Undergoing Surgical Resection

“…Using in situ hybridization increased miR-21-5p expression was found in 79% of PDAC; however, only 8% of benign pancreas and 27% of chronic pancreatitis tissue expressed this miRNA suggesting its important role in the development of PDAC (18). Very recently, serum level of miR-21-5p was confirmed to be sensitive and specific diagnostic biomarker of PDAC also in meta-analysis of 9 previous studies (19). MiR-155 was previously shown to be up-regulated in PDAC tumour tissue (20).…”

Personalized RNA Medicine for Pancreatic Cancer

“…Upregulation of miR-21 in tumor and stromal tissues is currently clearly associated with several gastrointestinal tumor types (pancreatic cancer, esophageal, gastric cancer, liver cancer; refs. 42, 43) and resistance to multiple anticancer agents (44) and is a promising noninvasive biomarker for pancreatic cancer risk and detection (24,45,46). As miR-21 is already a key detectable biomarker for PDAC (27,47,48), in a future phase I clinical trial, we propose to prospectively identify patients presenting with a similar miRNA signature that could be eligible for this biomarker-based RNA therapy.…”

Sources to variability in circulating human miRNA signatures

“…2 Applying different experimental techniques miRNA expression profiles have been associated to literally all diseases. Examples include Acute Myocardial Infarction (AMI), 6 Alzheimer Disease, 3 Bladder cancer, 7 lung cancer, 4,5 endocrine cancers, 8 gastric cancer, 6 pancreatic cancer, 7 glioma, 89 and many others. 10 In these studies, genome wide high-throughput profiles of miRNAs are usually done using microarrays or next-generation sequencing.…”