PGI and PGII are main progastricsins in the stomach, which closely reflects functional and morphological changes of gastric mucosa [15, 16]. In the present study, we found that in situ levels of PGI, PGII and PGI/II ratio consistently decreased in sequence of NOR/GS- > GA- > GC, especially in GA and GC. The youngers exhibited higher levels of PGI, PGII and PGI/II ratio than the olders. Interestingly, we found statistical correlations between in situ and serum levels of PGI/II ratio in GA cases and between PGI and PGII no matter in situ or in serum. There was lack of statistical correlation between in situ and serum expressions of PGI or PGII alone in this study.
It is widely accepted that the carcinogenesis process of gastric cancer progresses stepwise from normal stomach, inflammation, precancerous conditions, and to carcinoma, as described by Correa’s cascade . In the sequence of NOR/GS- > GA- > GC, consistently decreasing tendencies of in situ levels of PGI, PGII and PGI/II ratio were observed in this study. Although both NOR and GS subjects showed an extremely high positive rate of 100% of in situ PGs expression, the strongly-positive rates in GS cases significantly declined. In mild gastritis, inflammation could stimulate the production of PGs by increasing gastrin secretion; while in severe gastritis, the intensive inflammation could reversely reduce the PGs production mainly owing to injured and reduced gastric glands . When it comes to GA, the positive rates of PGs expression decreased sharply, probably because the decreasing number of glands and prolonged inflammation response in GA could impair normal gland function and synthesizing capability of PGs-producing cells. Further, the synthesis function would substantially lose in intestinal metaplasia cells or cancerous cells.
A proportion of severe and extensive chronic GA could evolve into severe dysplasia and even gastric carcinoma . Thus, the early diagnosis of GA is crucial for slowing down the malignant progression process of gastric mucosa. However, in clinical practice there is still certain difficulty in the early recognition of atrophy and cancerous lesions among pathologists based on haematoxylin-eosin staining of gastric biopsy. In this study, we found that only partial normal cells of remaining gastric glands in GA cases exhibited weak or moderate staining of PGI and PGII, while no PGs staining was detected in the lesions with severe atrophy, intestinal metaplasia or carcinoma. Previously, Waalewijn RA et al.  reported that PGI mRNA level in gastric cancer tissue was relatively low. StemmerMann GN et al.  showed that only 4.5% of well-differentiated intestinal-type GC and none of diffuse-type GC was PGI-positive staining. Our previous study also demonstrated that the positive rates of PGII expression decreased gradually in sequence of benign lesions, precancerous lesions and gastric cancer . These observations strongly suggested that the detection of in situ PGs expression may be important auxiliary biomarkers for the recognition of the location of atrophy and carcinoma.
Serum PGs have been widely used as biomarkers for GC or GA in clinical practice [3–7]. However, the question of whether the PGs expression changes in situ are synchronistic with those in serum is still unclear. In the present study, we explored the correlations between in situ and serum expressions of PGs (including PGI, PGII and PGI/II ratio) and between PGI and PGII expressions (including in situ and in serum). However, there was lack of correlations between in situ and serum expressions of PGI or PGII in this study. One of the possible reasons for negative correlations between in situ and serum expression of PGI or PGII may be that the majority of PGs production are restricted to gastric mucosa, and only about 1% are released into blood, which may lead to nonsynchronous alterations between in situ and serum PGs expressions . Another possible reason is that, apart from the influence of PGs production in stomach, the inflow of PGs from gastric epithelial cell to blood may be affected by other potential factors, such as different damage degrees of gastric epithelial cells, different vascular permeability, and different metabolic mechanisms between in situ and serum PGs . Interestingly, we observed a borderline correlation in the total study sample and a statistical correlation in GA cases between in situ and serum levels of PGI/II ratio. This observation indicated that in the subjects with precancerous diseases, the serum level of PGI/II ratio, rather than serum levels of PGI or PGII alone, may be a better index that reflects the decreasing tendencies of both PGI and PGII expression in situ. This may partially explain why serum level of PGI/II ratio showed a more close correlation with GC and GA but not serum PGI or PGII alone. In addition, we found that the PGI expression correlated well with PGII expression in situ and in serum, which indicated that PGI and PGII levels change simultaneously regardless of the status of gastric mucosa. In other words, synchronous changes of PGI and PGII expressions in situ or in serum may specifically reflect the damage of gastric mucosa. However, further studies with large-scale samples are still required to validate our findings.
We are aware that there are several limitations in this study. First, the study sample size of each disease group is relatively small, which limits our stratification analysis based on different histological classifications or severity degrees. Second, only a single method was used to detect the status of H. pylori infection in this study population; therefore, we only evaluated the potential influence of different status of H. pylori serology on the in situ PGs expression. Third, in this study we only investigated PGs expression in four sequentially-evolved groups of gastric mucosa, i.e. NOR, GS, GA and GC. A longtime follow-up study of PGs expression in situ as well as in serum in the same subjects whose stomach mucosa underwent sequential changes of NOR- > GS- > GA- > GC. Further study will be required to confirm our findings and to better guide the further use of PGs in future clinical practice.