Clinicopathological significance of claudin 4 expression in gastric carcinoma: a systematic review and meta-analysis

Background: The prognostic significance of claudin 4 (CLDN4) in patients with gastric cancer (GC) is controversial. This meta-analysis aims to assess the correlation between CLDN4 expression and clinicopathological characteristics and assess the prognostic significance of CLDN4 in GC. Methods: We searched the PubMed and Embase databases. We performed the meta-analysis with odds ratio (OR), hazard ratio (HR), and 95% confidence interval (CI) as effect values. Results: Fourteen studies containing 2,106 patients with GC were analyzed. The overall analysis showed that CLDN4 expression was associated with increasing pT category, tumor size, and lymph node metastasis in patients with GC (pT3-T4 vs pT1-T2: OR = 1.56, 95% CI = 1.13-2.16; P<0.01; large tumor size vs small tumor size: OR = 1.64, 95% CI = 1.15-2.34; P<0.01; positive lymph node metastasis vs negative lymph node metastasis: OR = 1.49, 95% CI = 1.12-1.97; P<0.01). CLDN4 expression was associated with histological differentiation (differentiated type vs undifferentiated type: OR = 2.90, 95% CI = 1.32-6.37; P = 0.01; Lauren intestinal type vs diffuse type: OR = 3.51, 95% CI = 1.48-8.28; P<0.01). CLDN4 expression was also strongly associated with sex and age. This meta-analysis found no significant association between CLDN4 expression and prognosis for overall survival in patients with GC (HR = 0.74, 95% CI = 0.43-1.27; P = 0.28). Conclusion: Present study indicates that aberrant CLDN4 expression plays an important role in the clinicopathological characteristics of GC.