Abstract
BackgroundThe identification of serial miRNAs targeting the same functional gastric protein could provide new and effective serological biomarkers for the diagnosis of gastric cancer (GC). The aim of this study was to evaluate the potential of miR-20a-5p, let-7a and miR-320a in the diagnosis of AG or GC and the correlation of the three miRNAs with their predicted target molecules PGA, PGC and PGA/PGC ratio.MethodsThe total of 291 patients included 103 controls (CON), 94 with atrophic gastritis (AG) and 94 with GC. The levels of serum miRNAs were detected by quantitative reverse transcription-polymerase chain reaction and serum pepsinogen A (PGA) and C (PGC) were determined by enzyme-linked immunosorbent assays.ResultsSerum miR-320a level decreased through the controls, AG and GC groups which were the cascades of GC development, while there were no significant differences in levels of miR-20a-5p and let-7a among the controls, AG and GC groups. When stratified by gender and age, serum miR-320a expression was lower in female GC patients than in controls (p = 0.035), especially in female GC patients older than 60 years (p = 0.008). For distinguishing female GC patients aged over 60, the area under the receiver operating characteristic curve for miR-320a was 0.699, and the best cut-off point was 4.76 with a sensitivity of 65.2% and specificity of 68.2%. Concerning the correlations between the selected miR-20a-5p, let-7a, miR-320a and PGs, we found that there were positive correlations between all the three and the ratio of PGA/PGC (r = 0.408, 0.255, 0.324; p = <0.001, 0.009, 0.001, respectively), but there was no relationship between the expression of serum miR-20a-5p and its predicted target PGA, or between let-7a and miR-320a and their predicted target PGC. Serum miR-320a was decreased and PGC was increased in the GC group compared with the control group.ConclusionsLevels of serum miR-320a were lower in female GC patients older than 60 than in controls, which may provide a potential valuable marker for diagnosing older women with GC. The levels of serum miR-20a-5p, let-7a and miR-320a were positively correlated with PGA/PGC, which may indirectly reflect the functional status of the gastric mucosa.
Highlights
The identification of serial miRNAs targeting the same functional gastric protein could provide new and effective serological biomarkers for the diagnosis of gastric cancer (GC)
Few studies have investigated the association between serum miRNAs and gastric diseases [8,9], several studies focused on the plasma miRNAs expression [10,11,12], Liu H et al identified miR-378 as a serum biomarker [8], and Liu R et al selected five miRNAs as a fingerprint for GC diagnosis [9]
Correlations between expression of serum miRNAs and gastric diseases There were no significant differences in the levels of miR-20a-5p and let-7a among the controls, atrophic gastritis (AG) and GC groups (p = 0.581, 0.445, respectively), but miR-320a levels decreased gradually among the different groups (4.99 ± 0.46 vs. 4.94 ± 0.45 vs. 4.90 ± 0.44, p = 0.152, Table 2)
Summary
The identification of serial miRNAs targeting the same functional gastric protein could provide new and effective serological biomarkers for the diagnosis of gastric cancer (GC). Few studies have investigated the association between serum miRNAs and gastric diseases [8,9], several studies focused on the plasma miRNAs expression [10,11,12], Liu H et al identified miR-378 as a serum biomarker [8], and Liu R et al selected five miRNAs (miR-1,-20a,-27a,-34 and −423-5p) as a fingerprint for GC diagnosis [9]. No attention has been paid to targeting of the same gene by serial miRNAs. But no attention has been paid to targeting of the same gene by serial miRNAs Such studies could help to clarify the common functions of serial miRNAs targeting individual genes and improve our understanding of their roles in gastric cancer (GC) and precancerous diseases
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