The Clinical Signification of Claudin-11 Promoter Hypermethylation for Laryngeal Squamous Cell Carcinoma

BACKGROUND Claudin-11 (CLDN11) is frequently silenced by its promoter hypermethylation. Previous studies have shown that CLDN11 promoter hypermethylation is a potential biomarker for diagnosing various cancers. The aim of this study was to investigate CLDN11 promoter methylation and its potential relevance to clinicopathologic features and prognosis of patients with laryngeal squamous cell carcinoma (LSCC). MATERIAL AND METHODS Using the quantitative methylation-specific polymerase chain reaction (qMSP), CLDN11 promoter methylation was measured in 91 tumor tissues and their paired adjacent normal tissues, and the relationship between CLDN11 methylation and clinicopathologic features was evaluated. A receiver operating characteristic (ROC) curve was created to assess diagnostic values, and the Kaplan-Meier survival analysis was used to evaluate the association between CLDN11 methylation and prognosis of patients with LSCC. RESULTS Our results showed significantly elevated promoter methylation of CLDN11 in tumor tissues compared to their adjacent tissues (p=1.227E-16). CLDN11 promoter methylation also increased in patients with lymph node metastasis (p=0.009), advanced clinical stage (p=9.26E-06) and higher T classification (p=0.003). The area under the ROC curve (AUC) of CLDN11 was 0.884 (95% CI=0.835-0.932, p<0.01). The Kaplan-Meier analysis indicated that high CLDN11 promoter methylation levels were associated with poor overall survival of LSCC patients (log-rank test, p=0.007). CONCLUSIONS We demonstrated that CLDN11 promoter hypermethylation is a frequent event in LSCC, and contributes to metastasis and progression of LSCC. Thus, CLDN11 could be a potential biomarker for diagnosis and prognosis of LSCC patients.