Claudin-18 Protein Linked to Poorer Survival in Colorectal Cancer

Claudin-18, a tight junction protein that has emerged as a therapeutic target in various gastrointestinal cancers, notably gastric adenocarcinoma, appears in a subset of colorectal tumors and marks patients who fare worse, according to a single-center retrospective immunohistochemical study of 107 colorectal cancer cases. The researchers detected Claudin-18 expression in 15.9% of tumors (17 of 107), while the remaining 84.1% showed negative or weak staining. This low prevalence underscores how incompletely the protein’s role in colorectal cancer has been understood.

Despite its rarity in this cohort, expression carried prognostic weight. Kaplan–Meier analysis showed significantly worse overall survival among patients with moderate or strong Claudin-18 staining compared with those whose tumors were negative or weak (log-rank p = 0.024). Mean overall survival was 121.0 months in the negative/weak group versus 76.6 months in the expressing group.

Event-free survival told a similar story. Patients with moderate or strong expression had significantly shorter event-free survival (log-rank p = 0.022), with mean event-free survival of 93.1 months in the negative/weak group versus 31.1 months among expressers. Progression-free survival showed a trend in the same direction, with poorer outcomes among patients with higher Claudin-18 expression, but the difference did not reach statistical significance (log-rank p = 0.066).

Notably, Claudin-18 expression did not correlate with any standard clinicopathological feature. The analysis found no significant associations with age, sex, tumor site, T stage, lymph node status, distant metastasis, TNM stage, histological subtype, or lymphovascular invasion (all p > 0.05). The picture became more complicated in multivariable modeling.

A binary logistic regression model including gender, age, lymphovascular invasion, tumor laterality, TNM stage, MSI status, histological type, and Claudin-18 expression was statistically significant overall (χ2(7) = 22.657, p = 0.002), yet none of the individual variables was independently associated with the outcome (all p > 0.05). Claudin-18 expression itself was not a significant predictor in the adjusted model (p = 0.931; odds ratio 0.63). The authors conclude that, although Claudin-18 expression was associated with poorer overall survival in this cohort, its independent prognostic value was not established.

Subject of Research: Claudin-18 expression and its prognostic significance in colorectal cancer

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

Article References: Al-Kabariti, A. Y., Abbas, M. A., Alashhab, M., Smarakan, S., & Sughayer, M. A. (2026). Claudin-18 expression is associated with poorer overall survival in colorectal cancer. PLOS One, 21(10), e0360740. https://doi.org/10.1371/journal.pone.0360740

Image Credits: AI Generated

DOI: 10.1371/journal.pone.0360740

Keywords: Claudin-18, colorectal cancer, immunohistochemistry, overall survival, event-free survival, prognosis, tight junction protein, retrospective study, biomarker, gastrointestinal cancer, expression, associated