Candidate microRNA Biomarkers in Human Gastric Cancer: A Systematic Review and Validation Study

Ji-Lin Wang,Ye Hu,Hao-Yan Chen,Xuan Kong,Jing-Yuan Fang,Jie Xu,Zhen-Hua Wang,William Cs Cho

doi:10.1371/journal.pone.0073683

Abstract

Gastric cancer (GC) remains a major cause of morbidity and mortality worldwide and there is therefore a clear need to search for more sensitive early diagnostic biomarkers. We performed a systematic review of eight published miRNA profiling studies that compared GC tissues with adjacent noncancerous tissues. A miRNA ranking system was used that took the frequency of comparisons, direction of differential expression and total sample size into consideration. We identified five miRNAs that were most consistently reported to be upregulated (miR-21, miR-106b, miR-17, miR-18a and miR-20a) and two miRNAs that were downregulated (miR-378 and miR-638). Six of these were further validated in 32 paired sets of GC and adjacent noncancerous tissue samples using real-time PCR. MiR-21, miR-106b, miR-17, miR-18a and miR-20a were confirmed to be upregulatedin GC tissues, while the expression of miR-378 was decreased. Moreover, we found a significant association between expression levels of miR-21, miR-106b, miR-17, miR-18a and miR-20a and clinicopathological features of GC. These miRNAs may be used for diagnostic and/or prognostic biomarkers for GC and therefore warrant further investigation.

Highlights

Despite a recent decrease in the incidence of gastric cancer (GC) [1], it remains a cause of major morbidity and mortality worldwide, especially in Eastern Asia
Endoscopy can detect the early stages of GC, most cases are still diagnosed at an advanced stage, which results in a poor prognosis [3]
Expressed miRNAs A total of 223 differentially expressed miRNAs were reported in the eight microarray studies (Differentially expressed miRNAs in each study were detailed in Table S1); 124 were upregulated in GC, and 99 were downregulated

Summary

Introduction

Despite a recent decrease in the incidence of gastric cancer (GC) [1], it remains a cause of major morbidity and mortality worldwide, especially in Eastern Asia. A total of one million new cases of GC occurred in 2008, with 738,000 deaths [2]. This accounts for 8% of the total cases of cancer and 10% of total deaths. Endoscopy can detect the early stages of GC, most cases are still diagnosed at an advanced stage, which results in a poor prognosis [3]. The 5-year survival rate for GC cases with stage II ranges from 30% to 50%, but falls to between 10% and 25% for patients with stage III disease [4]. Endoscopic techniques are developing rapidly, their value for the early detection of GC is limited due to a lack of sensitivity, high costs and inconvenience. New diagnostic and prognostic biomarkers for GC are urgently required

Methods

Results

Conclusion