Objective  To investigate the correlation between the expression level of Claudin18.2 in gastric adenocarcinoma tissues and clinicopathologic characteristics, histopathologic subtype, and other molecular markers, as well as its association with patient prognosis.

Methods  Database searches were performed to analyze Claudin18 (CLDN18) gene expression in gastric adenocarcinoma and to examine its associations with immune cell infiltration and prognosis. A total of 103 patients were enrolled. These patients were diagnosed with gastric adenocarcinoma at Chengdu Fifth People's Hospital between January 2021 and January 2023. Immunohistochemistry (IHC) was performed to assess Claudin18.2 expression in gastric adenocarcinoma tissue and adjacent tissues, and the associations between Claudin18.2 expression levels and the baseline parameters of the patients was analyzed accordingly. Kaplan-Meier analysis was performed to evaluate the associations of Claudin18.2 expression with overall survival (OS) and relapse-free survival (RFS) in patients with gastric adenocarcinoma. Cox regression analysis was performed to identify factors associated with adverse prognosis in patients with gastric adenocarcinoma.

Results  Database analysis showed that CLDN18 was expressed in a variety of tumors, mainly observed in gastric adenocarcinoma. No significant difference in CLDN18 expression was observed among gastric adenocarcinoma tissues in different clinical stages (P > 0.05). There was a positive correlation between CLDN18 expression and the infiltration of CD8⁺ T cells, neutrophils, and dendritic cells (P < 0.05). IHC findings showed that the positivity rate of Claudin18.2 protein expression in gastric adenocarcinoma was 56.3%, with a high expression rate of 37.9%, and the positive expression of Claudin18.2 was mainly associated with lymph node metastasis, human epidermal growth factor receptor 2 (HER2) protein expression, and Epstein-Barr virus (EBV) infection (P < 0.05). High expression of Claudin18.2 was mainly associated with the degree of tumor differentiation, lymph node metastasis, the intestinal and undefined types according to the Lauren subtype classification, P53 mutation status, and EBV infection (P < 0.05). Both the database analysis and follow-up of the enrolled patients with gastric adenocarcinoma showed no significant association between Claudin18.2 expression and either RFS or OS (P > 0.05). Cox multivariate analysis showed that clinical stage Ⅲ and Ⅳ (OS: hazards ratio HR = 5.769, 95% CI: 1.039-32.016; RFS: HR = 5.347, 95% CI: 1.094-26.131) abnormal tumor marker levels at 6 months after surgery (OS: HR = 0.436, 95% CI: 0.224-0.852; RFS: HR = 0.466, 95% CI: 0.230-0.941) were independent risk factors affecting OS and RFS in patients (P < 0.05).

Conclusion  Claudin18.2 is highly expressed in gastric adenocarcinoma tissues, and the expression is associated with lymph node metastasis and EBV-associated gastric cancer. Although the prognostic value of Claudin18.2 remains unclear, it may be expected to become a new molecule for targeted therapy and an important target for diagnosis of specific types of gastric cancer.