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

Abstract

BackgroundClaudin-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/MethodsUsing 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.ResultsOur 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).ConclusionsWe 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.

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“…Epidemiologic data indicated that epigenetic and genetic alterations, and environmental and lifestyle-related factors, such as tobacco, alcohol, and viral infection contributed to the pathogenesis of LSCC [ 19 ]. Chemoresistance is one of the major obstacles in the chemotherapeutic treatment of LSCC [ 20 , 21 ], and accumulating studies have demonstrated that dysregulation of lncRNAs is implicated with chemoresistance in cancers [ 22 , 23 ].…”

Comprehensive analysis of expression and prognostic value of the claudin family in human breast cancer

“…Downregulation of claudin-5 increased the permeability of the blood–tumor barrier [ 54 , 55 ], suggesting it could prevent brain metastasis. Low CLDN11 expression has been used as a prognosis biomarker in certain cancers [ 56 – 58 ]. Moreover, miR-99b-induced downregulation of CLDN11 promoted metastasis of hepatocellular carcinoma [ 59 ].…”

“…Interestingly, we found that CLDN11 was hypomethylated in BC with lower mRNA expression than in normal tissues. Methylation of CLDN11 promoter is known to be associated with the development and poor survival in several cancers [ 56 – 58 ]. Moreover, miRNA-induced reduced expression of CLDN11 promoted metastasis [ 59 , 60 ], implying DNA methylation as one of the underlying regulatory mechanisms of at least certain claudins in BC.…”

Extracellular Vesicles Containing MicroRNA-92a-3p Facilitate Partial Endothelial-Mesenchymal Transition and Angiogenesis in Endothelial Cells

“…Subsequently, claudin-11/OSP expression in endothelial cells and its barrier function has also been demonstrated [13,14]. Recent studies have shown that the downregulation of CLDN11/OSP contributes to the malignancy of various cancers, as indicated by an increased degree of invasiveness, metastasis promotion, and poor prognoses in colon cancer [15], gastric cancer [16], and laryngeal squamous cell carcinoma [17] while the forced expression of CLDN11/OSP in bladder cancer decreases the degree of invasiveness [18]. Those studies demonstrated that the decreased expression level of CLDN11/OSP in cancer is due to the hypermethylation of its promoter region.…”