Claudin18.2 expression in gallbladder cancer correlates with immune activation and a favourable prognosis.

Abstract

Aims: Gallbladder carcinoma (GBC) is frequently diagnosed and treated in advanced stages and has a poor prognosis. Recent studies have identified claudin18.2 (CLDN18.2) as a promising target in digestive system cancer. In this study, we aimed to determine the expression of CLDN18.2 and its correlation with clinicopathological characteristics in patients with GBC.

Methods: The expression of CLDN18.2 of 228 patients with GBC was studied via immunohistochemistry. Immunostained samples were evaluated according to the H-score. The samples were divided into low/negative (H-score=0-49) and high/positive (H-score=50-300) expression groups. The correlations between CLDN18.2 and various clinicopathological characteristics, including survival, were assessed. Multiplex immunofluorescence and image acquisition were used to analyse the relationship between CLDN18.2 expression and the immune microenvironment.

Results: The overall positive CLDN18.2 staining rate was 39.91% (91/228); 137 (60.08%) were given 0 points, 30 (13.15%) were given 1 point, 28 (12.28%) were given 2 points and 33 (14.47%) were given 3 points. Low CLDN18.2 expression was correlated with adverse prognostic factors, including poor differentiation, deep infiltration depth, lymph node metastasis and distant metastasis. High CLDN18.2 expression was associated with better survival. Furthermore, the distribution of immune cell subsets significantly differed between the high and low CLDN18.2 expression groups.

Conclusions: The correlations between the expression of CLDN18.2 and clinicopathological characteristics and prognosis suggest that early-stage patients could benefit more from future anti-CLDN18.2 treatment and that CLDN18.2 may function as a pivotal regulatory molecule in patients with GBC. The underlying mechanism may be related to immune activation caused by high CLDN18.2 expression.