Recent findings have presented serum/plasma miRNAs as potential biomarkers for several disease conditions, including human cancers [28–31]. However, studies of serum miRNAs in relation to gastric diseases have been limited, and no attention has been paid to miRNAs serially targeting the same gene. Based on a series of miRNAs predicted by bioinformatic software to target to PGA and/or PGC, we selected miR-20a-5p, let-7a and miR-320a for further study. We investigated 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. The expression of miR-320a was lower in older female GC patients than in controls, suggesting that miR-320a may prove a valuable marker for diagnosing older women with GC. miR-20a-5p, let-7a and miR-320a were positively correlated with the PGA/PGC ratio, which could indirectly reflect the functional status of the gastric mucosa.
Several studies have identified tumour-specific miRNAs alterations in plasma/serum of cancer patients, and have shown the potential of circulating miRNAs as new non-invasive biomarkers for cancer screening [12, 32]. The results of our study indicated no differences in serum miR-20a-5p and let-7a levels among the controls, AG and GC groups, while miR-320a expression fell throughout the controls, AG and GC groups. Serum miR-320a levels were lower in female GC patients than in controls, and this difference was especially marked in older women, aged over 60, suggesting that miR-320a may be a new clinical biomarker for GC diagnosis with population specificity. Studies of miR-320a to date have been limited to its roles in regulating the physiological functions of the blood–brain barrier , and in intrahepatic cholangiocarcinoma [34, 35], colon cancer  and childhood leukaemia . To the best of our knowledge, the current study is the first to report that miR-320a could act as a serum biomarker of GC, especially in older women. Although few studies have investigated its mechanisms, some have reported a relationship between its predicted target PGC and gender, while others reported that the PGA/PGC ratio was related to age, but only in women [38, 39]. Software has also predicted that miR-320a targets the estrogen-related receptor gamma (http://www.targetscan.org/cgi-bin/targetscan/mamm_31/targetscan.cgi?species=Human&gid=&mir_c=&mir_nc=&mirg=hsa-miR-320). These lines of evidence all suggest that miR-320a may play an important role in the development of GC in women, and could indirectly reflect the functional state of the gastric mucosa. Its use as a biomarker would be associated with the advantages of non-invasion, low cost and higher stability. However, further studies in larger samples are needed to clarify its mechanisms and verify its use as a biomarker in older women with GC. Of course, the changes of miRNAs maybe not only related with the changes of gastric mucosal function conditions, but also related with some other factors, for examples anemia , the stimulus of pathogenic microorganism such as H.pylor  i, some proteins involved in miRNAs processing pathway like Drosha, Dicer and Argonaute [42, 43]. The other factors related should be considered in the further studies in the future.
Serum PGA and PGC levels seem to be related to gastric mucosal glandular and cellular quantities, and also indirectly reflect the secretary function of the gastric corpus and/or gastric antrum. PGA is secreted from the gastric corpus and gastric angle, while PGC is secreted from all the stomach, including the corpus, angle and antrum. A decline in the PGA/PGC ratio reflects the development of atrophic lesions on the gastric mucosa , and a low PGA/PGC ratio is related to a high risk of GC [38, 44, 45]. This has therefore been used as an effective parameter for screening individuals at high risk of GC in the population, and may be a clinically useful biomarker of GC and precancerous diseases such as AG [16, 38, 46, 47]. Broutet et al. reported that although PGC was secreted from different sites in the stomach, it was related to PGA; while PGA increased rapidly, PGC varied slightly, and the correlation coefficient reached 0.75 . The current study also calculated a correlation coefficient between PGA and PGC of 0.727. This relationship may explain why the PGA/PGC ratio reflects the functional status of the gastric mucosa more precisely than either PGA or PGC alone. Our study found no relationship between the expression of miR-20a-5p and PGA, let-7a and PGC, or miR-320a and PGC, but there were positive correlations between each of the three and the PGA/PGC ratio which was already known as a useful biomarker for disease diagnosis, and the studied miRNAs were synchronous with the known PGA/PGC ratio suggesting their potential as useful biomarkers for disease diagnosis.
Considering H. pylori is an important environmental factor in the stomach which is also a class Icarcinogen defined by World Health Organization (WHO), we analysis the three miRNAs in the HP stratification among different gastric diseases, but found no difference. Whether H.pylori and/or other environmental factors affect this association needs more studies in larger samples in the future.
There was some limitation in our study. First, the selected miRNAs may functionally target PGA/C and/or at least was only proof by the bioinformation software, some evidence for the further functional experiments are needed. Secondly, correlation of expression in the tissue of miRNAs and its predicted target protein is needed for further investigation. Thirdly, the correlation of miRNAs expression and clinicopathological characteristics of patients with gastric cancer, such as Borrmann’s classification, growth pattern, TNM stage, invasion depth and lymph node metastasis,et al. were not further analyzed because of biopsy-limited information missing. Fourth, the source of controls was not the normal population but with a minimal superficial gastritis according to the pathological diagnosis, and gastritis was also belongs a cascade of GC development.