During H. pylori-induced atrophic gastritis, the gastric environment undergoes substantial remodeling.1 Current gastric cancer guidelines emphasize endoscopic and pathological assessment in the diagnostic work-up of established disease.2 Antralization of the gastric mucosa, in which oxyntic body epithelium adopts an antral-like phenotype, is identified by histopathological examination of gastric biopsy specimens.3 Previous histopathological studies have described antral-type mucosa in the gastric incisura and more proximal gastric sites and its association with H. pylori infection and intestinal metaplasia.4,5 The possible role of H. pylori-induced antralization in gastric carcinogenesis has also been discussed.6 More broadly, some H. pylori-associated atrophic gastric changes may regress after eradication therapy.7 Blood protein biomarkers are being investigated as potential adjuncts for detecting gastric preneoplastic and cancerous lesions.8 Economical, convenient, and non-invasive testing methods suitable for broader population-level application remain needed.
The present study by Ye et al.3 reported associations between antralization and alterations in both peripheral blood parameters and gastric mucosal markers. These include elevated peripheral lymphocyte counts, reduced serum lipopolysaccharide (LPS) levels, increased expression of trefoil factor-2 (TFF2) and mucin 6 (MUC6), decreased expression of MUC5AC in the proximal gastric mucosa, and higher MUC5B staining intensity specifically in the gastric body mucosa. The findings suggest that these markers may be associated with antralization in the studied population. Current or past Helicobacter pylori (H. pylori) infection was also more common among patients with antralization. The study’s prospective design and the use of pathological confirmation as the diagnostic gold standard provide a useful basis for further investigation. The findings can be considered as two preliminary profiles: a systemic circulatory profile and a local tissue-specific mucin profile.
The identification of higher peripheral blood lymphocyte counts coupled with lower serum LPS levels in the antralization group is intriguing. The higher lymphocyte count may reflect a sustained, albeit dysregulated, immune response to chronic H. pylori-driven inflammation, a well-known driver of antralization and metaplastic changes. The biological basis of the lower serum LPS level remains unclear and was not investigated in the study. However, the reported diagnostic performance of the individual blood markers was modest, and no combined model was developed or independently validated. These findings support further evaluation of lymphocyte count and LPS as candidate blood-based markers rather than their current use for screening, risk stratification, or clinical decision-making.3
The detailed analysis of mucin and trefoil factor expression provides a molecular correlate to the histological changes of antralization. The down-regulation of MUC5AC (a mucin characteristic of normal gastric surface epithelium) and the up-regulation of TFF2 and MUC6, together with higher MUC5B staining intensity specifically in the gastric body mucosa, delineate a tissue expression pattern associated with this process. This “mucin switch” may provide candidate immunohistochemical markers for further evaluation.3
The blood and gastric tissue findings reported by Ye et al.3 warrant further validation. The blood-based markers are potential non-invasive candidates, whereas the tissue markers are biopsy-based histological correlates. The findings on lymphocyte counts and LPS levels support further evaluation of blood-based markers of antralization.3 At the tissue level, the tissue marker pattern (TFF2 and MUC6 up-regulation; MUC5AC down-regulation; and higher MUC5B staining intensity specifically in the gastric body mucosa) may, upon validation, serve as a candidate histological marker. TFF2 is a characteristic marker of SPEM, although whether TFF2-related pathways have mechanistic or therapeutic relevance remains to be determined.9 Further work is needed to determine whether these tissue changes have value for early detection or disease monitoring. Although previous studies have linked increased Ki-67 and BCL-2 expression to antralization,10 the underlying regulatory mechanisms remain largely unexplored. Investigating these pathways may clarify the biological significance and potential reversibility of antralization-related changes.
Despite these promising insights, the current study has limitations. The cohort size is modest, underscoring the need for validation in larger, multi-ethnic populations. The single-center cohort consisted of symptomatic patients undergoing endoscopy and included no healthy control group, which limits generalizability to asymptomatic population-based screening. The association with H. pylori infection also raises the question of whether the observed biomarker patterns are present in H. pylori-negative antralization. Moreover, the study establishes an association but not causality between lymphocyte counts, LPS levels, and antralization, pointing toward a critical direction for future mechanistic research. Finally, further biomarker discovery and validation using complementary approaches will be needed to identify additional markers and assess combinations of markers.
In conclusion, the study by Ye et al.3 provides preliminary evidence that peripheral blood measures and gastric tissue marker patterns are associated with antralization. These findings support further investigation of candidate blood-based markers and biopsy-based histological correlates. Larger, independent studies are needed to establish diagnostic performance and clinical utility before these markers are used for screening, risk assessment, or monitoring.
Declarations
Funding
None.
Conflict of interest
Dr. Lihua Ren serves as an Early Career Editor of Cancer Screening and Prevention. Dr. Ren was not involved in the editorial review or decision-making process for this article. The other authors have no conflicts of interest to declare.
Authors’ contributions
Drafting of the manuscript (JS), critical revision of the manuscript (LR, HC). All authors read and approved the final manuscript.