Novel diagnostic value of circulating miR-18a in plasma of patients with pancreatic cancer

Abstract

Background:Several recent studies have demonstrated that microRNAs (miRNAs) are stably detectable in the plasma/serum. We hypothesised that miR-18a in the plasma is a potential biomarker in patients with pancreatic cancer.Methods:miR-18a is located in the miR-17–92 cluster and reported to be highly expressed in pancreatic cancer tissues. This study was divided into three parts: (1) Confirmation of higher miR-18a levels in primary pancreatic cancer tissues and cell lines than in normal pancreatic tissues and a human fibroblast cell line. (2) Evaluation of the plasma miR-18a assay using quantitative RT–PCR by comparing plasma results obtained from 36 patients with pancreatic cancer and from 30 healthy volunteers. (3) Evaluation of the assay for monitoring tumour dynamics in patients with pancreatic cancer.Results:(1) The expression of miR-18a was significantly higher in pancreatic cancer tissues (P=0.012) and pancreatic cancer cell lines (P=0.015) than in normal tissues and fibroblasts. (2) Plasma concentrations of miR-18a were significantly higher in pancreatic cancer patients than in controls (P<0.0001). The value of the area under the receiver-operating characteristic curve (AUC) was 0.9369. (3) Plasma levels of miR-18a were significantly lower in postoperative samples than in preoperative samples (P=0.0077).Conclusion:Circulating miR-18a might provide new complementary tumour markers for pancreatic cancer.

Relevance of microRNA‐18a and microRNA‐199a‐5p to hepatocellular carcinoma recurrence after living donor liver transplantation

“…(29) Thus, increased plasma miR-18a might also serve as a novel marker for HCC recurrence after LDLT. In the present study, all patients were under immunosuppression after LT.…”

MicroRNA screening identifies circulating microRNAs as potential biomarkers for osteosarcoma

“…Following the initial demonstration that elevated serum levels of miRNA-21 were associated with relapse-free survival of diffuse large B-cell lymphoma patients (13), several circulating miRNAs were identified as potential diagnostic and prognostic biomarkers for various types of cancer, including nasopharyngeal carcinoma (14) and glioma (15), as well as breast (6,16,17), gastric (18,19), prostate (20,21), pancreatic (22) and colorectal cancer (23). As a tumor screening marker, circulating miRNAs have several advantages, including the availability of serum samples and their stability during storage relative to that of tissue samples.…”

Circulating microRNA profiles in plasma: identification of miR-224 as a novel diagnostic biomarker in hepatocellular carcinoma independent of hepatic function

“…Moreover, compared to serum, plasma might retain higher protein levels, including those of coagulant-related proteins. These finding prompt us to consistently use plasma miRNAs in future clinical application [25,[34][35][36][37][38][39][40][41][42][43][44]. Indeed, miRNA profiles and miRNA concentrations were considerably different between serum and plasma.…”

“…A volume of 400 μl of plasma was used as the common denominator in each microarray analysis; thus, there was no definite internal control in the plasma miRNA analyses as shown in previous studies [34][35][36][37][38][39][40][41]. Total RNA was also extracted from four 15-μm-thick slices of the formalin-fixed and paraffin-embedded tissue samples (60 μm thickness) using a Recover All Total Nucleic Acid Isolation Kit (Ambion) and subsequently eluted into 60 μl of Elution Solution according to the manufacturer's instructions.…”

“…These findings have prompted the identification of novel liquid biomarkers of miRNAs in cancers. We have previously identified cancer-associated miRNAs in plasma, which might be useful for the detection of cancer, monitoring of tumors, prediction of malignant potential, and prognosis and chemoresistance in gastric, esophageal and pancreatic cancers [25,[34][35][36][37][38][39][40][41][42][43][44].…”