Abstract
BackgroundTo investigate the potential of serum miRNAs as biomarkers for early detection of gastric cancer (GC), a population-based study was conducted in Linqu, a high-risk area of GC in China.Methodology/Principal FindingsAll subjects were selected from two large cohort studies. Differential miRNAs were identified in serum pools of GC and control using TaqMan low density array, and validated in individual from 82 pairs of GC and control, and 46 pairs of dysplasia and control by real-time quantitative reverse transcription-polymerase chain reaction. The temporal trends of identified serum miRNA expression were further explored in a retrospective study on 58 GC patients who had at least one pre-GC diagnosis serum sample based on the long-term follow-up population. The miRNA profiling results demonstrated that 16 miRNAs were markedly upregulated in GC patients compared to controls. Further validation identified a panel of three serum miRNAs (miR-221, miR-744, and miR-376c) as potential biomarkers for GC detection, and receiver operating characteristic (ROC) curve-based risk assessment analysis revealed that this panel could distinguish GCs from controls with 82.4% sensitivity and 58.8% specificity. MiR-221 and miR-376c demonstrated significantly positive correlation with poor differentiation of GC, and miR-221 displayed higher level in dysplasia than in control. Furthermore, the retrospective study revealed an increasing trend of these three miRNA levels during GC development (P for trend<0.05), and this panel could classify serum samples collected up to 5 years ahead of clinical GC diagnosis with 79.3% overall accuracy.Conclusions/SignificanceThese data suggest that serum miR-221, miR-376c and miR-744 have strong potential as novel non-invasive biomarkers for early detection of GC.
Highlights
Gastric cancer (GC) is the second leading cause of cancer death in the world, with nearly half occurring in China [1,2]
Subject characteristics A total of 82 gastric cancer (GC) patients, 46 subjects with DYS, and 128 controls with superficial gastritis (SG) or mild chronic atrophic gastritis (CAG) were included in this study
First-stage validation The expressions of 16 candidate miRNAs were measured in individual serum samples of 14 GCs and controls that were used for array test
Summary
Gastric cancer (GC) is the second leading cause of cancer death in the world, with nearly half occurring in China [1,2]. Early detection of GC is a key measure to reduce the mortality and improve the prognosis of GC. Gastroscopic screening for GC is highly reliable, it is invasive and costly, for the developing countries. Much effort has been made to develop less expensive preliminary screening tests in accessible specimens. Many previously investigated analytes, such as pepsinogen (PG) I/II ratio, carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA 19-9), were not sensitive and specific enough for GC screening [3,4]. There is an urgent need for new noninvasive biomarkers to improve the early detection of GC. To investigate the potential of serum miRNAs as biomarkers for early detection of gastric cancer (GC), a population-based study was conducted in Linqu, a high-risk area of GC in China
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