Claudin-18 expression is associated with poorer overall survival in colorectal cancer

Claudin 18, a tight junction protein, has emerged as a therapeutic target in various gastrointestinal cancers, notably gastric adenocarcinoma. However, its prevalence and clinicopathological significance in colorectal cancer (CRC) remain incompletely understood. In the current single-center, retrospective, immunohistochemical study, the prevalence and prognostic value of Claudin-18 was investigated in CRC. Claudin-18 expression was detected in 15.9% (17/107) of CRC cases, with negative/weak expression in 84.1% (90/107). No significant associations were observed between Claudin-18 expression and age, sex, tumor site, T stage, lymph node status, distant metastasis, TNM stage, histological subtype, or lymphovascular invasion (all p > 0.05). No significant associations were identified between Claudin-18 expression and age, sex, tumor location, histological subtype, or TNM stage. Furthermore, Claudin-18 expression independently predicted survival outcomes in CRC where Kaplan-Meier analysis demonstrated significantly worse overall survival (OS) in patients with strong/moderate Claudin-18 expression compared with Claudin-18 -negative/weak expression (log rank test, p = 0.024). Mean OS was markedly longer in Claudin-18 -negative/weak expression group (121.0 vs.76.6 months). Progression-free survival (PFS) analysis demonstrated a trend toward poorer outcomes among patients with increased Claudin-18 expression; however, the difference did not reach statistical significance (log-rank test, p = 0.066). Event-free survival (EFS) was also significantly reduced in patients with strong/moderate Claudin-18 expression (log-rank test, p = 0.022). Mean EFS was markedly longer in CLDN18 negative/weak expression (93.1 vs. 31.1 months). Multivariable binary logistic regression showed that the overall model was statistically significant (χ2(7) = 22.657, p = 0.002). However, none of the evaluated variables-including gender, age, lymphovascular invasion, tumor laterality, TNM stage, MSI status, histological type, and Claudin-18 expression-was independently associated with the outcome (all p > .05). Claudin-18 expression was not a significant predictor in the adjusted model (p = 0.931; OR = 0.63). In conclusion, despite its low prevalence in the current cohort, Claudin-18 expression was associated with poorer overall survival; however, its independent prognostic value was not established.