Low expression of claudin-4: an indicator of recurrence in esophageal squamous cell carcinoma after Ivor Lewis esophagectomy?

The high recurrence rate after surgery is the main reason for the poor prognosis of esophageal squamous cell carcinoma (ESCC) patients. Finding indicators of recurrence and taking adjuvant therapy may be useful for patients in high risk of recurrence. claudin-4 (CLDN4) is the core protein to form the tight junction, which plays an important role in cell adhesion, and its aberrant expression were detected in various cancers while its expression and functions in ESCC still remained unclear. Here, we detected the expression of CLDN4 in 114 ESCC tissue samples by real-time RT-PCR and immunohistochemistry, and the result showed that the low expression of CLDN4 correlated with a higher T staging (P = 0.010), lymphatic metastasis (P < 0.001) and recurrence status (P = 0.002). And the Cox regression analysis showed that the T classification (P = 0.005), lymph node metastasis (P = 0.003) and low CLDN4 expression (P = 0.029) were independent risk factors of recurrence. Further, we proved the CLDN4 in inhibiting growth, colony formation and invasion in vitro by establishing two stable CLDN4-silencing ESCC cell lines. In conclusion, CLDN4 played an important role in preventing metastasis and could be an effective biomarker to predict the recurrence of ESCC.