Upregulated Claudin-18.2 Is a Poor Prognostic Indicator for Rectal Cancer Patients Undergoing Preoperative Concurrent Chemoradiotherapy

Introduction: Claudins are essential for tight junctions, maintaining cell adhesion, regulating intercellular molecule movement, and preserving cellular polarity. Altered claudin expression can lead to dysfunctions, potentially contributing to oncogenesis in epithelial cancers. The role of CLDN18.2 in rectal cancer is not well understood. Methods: We analyzed tissue samples from 343 rectal cancer patients who underwent concurrent chemoradiotherapy (CCRT) followed by proctectomy. Results: Upregulated CLDN18.2 expression was associated with older age (p = 0.016), higher pre-CCRT tumor N stage (p = 0.014), higher post-CCRT tumor T stage (p = 0.005), more vascular invasion (p = 0.008), and worse tumor regression (p < 0.001). Univariate analysis showed high CLDN18.2 expression correlated with worse disease-free survival (p < 0.0001), local recurrence-free survival (p < 0.0001), and metastasis-free survival (p < 0.0001). Multivariate analysis indicated high CLDN18.2 expression was associated with inferior disease-specific survival (p < 0.001) and metastasis-free survival (p < 0.001). Conclusion: Elevated CLDN18.2 expression is associated with adverse clinical outcomes and pathological features, yet suggests a more unfavorable treatment response in rectal cancer patients undergoing CCRT, indicating its potential as a biomarker.