Identification of circulating microRNAs for the diagnosis of early-stage gastric cancer.

Abstract

33 Background: The development of gastric cancer (GC) is a stepwise progression from non-active gastritis (NAG), chronic active gastritis (CAG) and precursor lesions of GC (PLGC: atrophy, metaplasia). Early detection of GC improves survival rates. Recent evidence has proposed circulating microRNAs (c-miRNAs) as biomarkers. The aim was to explore the c-miRNA profile of a cohort of non-GC and GC patients in order to identify early biomarkers of GC. Methods: Thirty-eight patients were enrolled: ten with NAG, nine with H. pylori infected with CAG, eight with PLGC, and ten with GC. GC patients were at TNM stages I and II. As quality controls, synthetic RNA was added during the isolation, cDNA synthesis, and PCR steps. MiRNA profiling was performed using Exiqon Human Panel I. Exploratory significance was set at P<0.05 with fold change (FC)≥1.6. Results: Of the total of 372 miRNAs analyzed, 154 miRNAs were detected in all samples. miR-185-5p was used to normalize. Compared to NAG individuals, GC patients showed downregulation of three miRNAs. GC patients also showed reduced expression of miR-205 compared to H.pylori-infected patients with CAG. Five miRNAs were upregulated in GC patients compared to PLGC patients (miR-134, miR-204, miR-224, miR-409, miR-877). Finally, in comparison with non-GC, seven miRNAs were found to be deregulated in GC patients (miR-130b, miR-144, miR-205, miR-219a, miR-224, miR-451a, miR-501). Specificities calculated at 90% sensitivity were low and significant FC ranged from -3.2 to 2.8. Conclusions: Using miRNA qPCR quantification, we found a deregulation of c-miRNAs in early GC. However, our results also show low diagnostic accuracy for early GC due to the small FC observed and the overlap in the miRNA levels between non-GC and GC patients. Further validation in a larger cohort and a prospective study is needed to determine conclusively whether these miRNAs serve as biomarkers. In our opinion, new methods need to be developed in order to quantify c-miRNAs and improve their diagnostic accuracy. [Table: see text]