Clinical impact of circulating miR-221 in plasma of patients with pancreatic cancer

Abstract

Background:Several recent studies have demonstrated that microRNAs (miRNAs) are stably detectable in plasma/serum. We tested miR-221 and miR-375, which are frequently reported to be highly and poorly expressed in pancreatic cancer (PCa), as candidates for plasma biomarkers in PCa.Methods:This study was divided into three parts: (1) Confirmation of higher miR-221 levels in primary PCa tissue and cell lines than normal pancreatic tissues. (2) Evaluation of plasma miR-221 and miR-375 concentrations by comparing results from 47 consecutive PCa patients and 30 healthy volunteers. (3) Evaluation of the assay for monitoring tumour dynamics in PCa patients.Results:(1) Expression of miR-221 was significantly higher in PCa tissues and cell lines than normal pancreatic tissues. (2) Plasma miR-221 concentrations were significantly higher in PCa patients than that in benign pancreatic tumours (P=0.016) and controls (P<0.0005), while plasma miR-375 concentrations tended to be lower in PCa patients (P=0.064), and the miR-221/miR-375 ratio was significantly higher (P<0.0001) in PCa patients than in controls. (3) Plasma miR-221 concentrations were significantly reduced in postoperative samples (P=0.018). Furthermore, PCa patients with high plasma miR-221 concentrations had significant correlation with distant metastasis (P=0.041), and non-resectable status (P=0.021).Conclusion:Plasma miR-221 could be a useful biomarker for cancer detection, monitoring tumour dynamics and predicting malignant outcomes in PCa patients, and may contribute to clinical decision making in PCa treatments.

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.…”

“…Next, 11 miRNAs previously reported as biomarkers in body fluids were excluded. We limited the target miRNAs to oncogenic miRNAs, as previous studies have revealed that high plasma levels of oncogenic miRNAs might be derived from tumor necrosis, apoptosis and the active release of secretory vesicles, such as exosomes, from cancer cells; thus, these miRNAs in plasma could reflect tumor dynamics in cancer tissues [34][35][40][41]. Tumorsuppressive miRNAs and functionally unknown miRNAs were excluded in the present study because the origin of these miRNAs is not well known [38].…”

“…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].…”

Microarray expression profile analysis of long non-coding RNAs in pancreatic ductal adenocarcinoma

“…Enormous efforts have been made to identify the special molecular markers for PDAC, which show vast application prospect as targets for the disease treatment. The research fields of molecular markers for PDAC include proteins, such as K-Ras, p16, and SMAD4 (3)(4)(5); miRNAs, such as miR-210 and miR-221 (6)(7)(8); and the recently research hotspot the lncRNAs.…”