Detection of gastric cancer-associated microRNAs on microRNA microarray comparing pre- and post-operative plasma

Abstract

Background:Recently, it was reported that plasma microRNAs (miRNAs) are low-invasive useful biomarkers for cancer. We attempted to isolate gastric cancer (GC)-associated miRNAs comparing pre- and post-operative paired plasma, thereby excluding the possible effects of individual variability.Methods:This study was divided into four steps: (1) microarray analysis comparing pre- and post-operative plasma; (2) validation of candidate miRNAs by quantitative RT–PCR; (3) validation study of selected miRNAs using paired plasma; and (4) comparison of the levels of selected miRNAs in plasma between healthy controls and patients.Results:From the results of microarray analysis, nine candidate miRNAs the levels of which were markedly decreased in post-operative plasma were selected for further studies. After confirmation of their post-operative marked reduction, two candidate miRNAs, miR-451 and miR-486, were selected as plasma biomarkers, considering the abundance in plasma, and marked decrease in post-operative samples. In validation, the two miRNAs were found to decrease in post-operative plasma in 90 and 93% of patients (both P<0.01). In comparison with healthy controls, the levels of both miRNAs were found to be significantly higher in patients, and the area under the curve values were high at 0.96 and 0.92.Conclusion:Plasma miR-451 and miR-486 could be useful blood-based biomarkers for screening GC.

Macrophage-secreted Exosomes Delivering miRNA-21 Inhibitor can Regulate BGC-823 Cell Proliferation

“…This is especially the case in Asia, with the highest incidence being found in China, Japan, and Korea (Ferlay et al, 2010;Saeki et al, 2013), and about 1,000,000 new cases every year (Yang, 2006). There is increased expression of miR-421, miR-21, miR-221/222, and miR-106a in gastric cancer, while the expression of miR-124a, miR-128b, miR-148, and miR-129 is reduced (Guo et al, 2009;Konishi et al, 2012). MiRNA-21 was one of the first miRNAs to be discovered in human cells, and its expression is significantly upregulated in different kinds of solid tumors, for instance breast and gastric cancer, and is closely associated with cancer pathogenesis (Huang et al, 2013).…”

MiR-421 Regulates Apoptosis of BGC-823 Gastric Cancer Cells by Targeting Caspase-3

“…Various miRNAs are differentially expressed in gastric cancer cells. miR-421, miR-21, miR-221/222, and miR-106a show increased expression in gastric cancer, while miR-124a, miR-128b, miR-148, and miR-129 show decreases in expression (Guo et al, 2009;Konishi et al, 2012). miR-421 target genes are down-regulated via miR-421 binding to the 3'UTR of ATM (Hu et al, 2010).…”

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.…”

“…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]. Consequently, 48 miRNAs were excluded.…”

“…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].…”