Aberrant promoter methylation of T-cadherin in sera is associated with a poor prognosis in oral squamous cell carcinoma

 Qiuju Wang, Yan Chen, Yibo Chen, Jian Jiang, Xiaoyu Song, Li Zhang, Qiao He, Bo Ye, Lichun Wu, Rui Wu, Qin Lai, Dongsheng Wang, Yanzhen Zhao

Abstract:

T-cadherin functions as a suppressor gene, which is frequently inactivated by aberrant promoter methylation in several human cancers, but its methylation status in oral squamous cell carcinoma (OSCC) has been scarcely studied. Thus this study aimed at exploring the clinical significance and prognostic value of T-cadherin methylation in sera of patients with OSCC. Methylation-specific PCR (MSP) and bisulfate sequencing PCR (BSP) was performed to examine the methylation status of T-cadherin. Then, the associations between methylation status of T-cadherin and various clinicopathological variables or patient survival were investigated in 202 patients with OSCC and 68 controls. T-cadherin methylation was detected in 62 out of 202 (30.7%) patients with OSCC, and the methylation status of T-cadherin in corresponding tissues was confirmed by BSP. Methylation of T-cadherin was significantly associated with advanced tumor T-stage (p<0.001) and N-stage (p=0.003), positive lymphatic metastasis (p=0.004) and tumor recurrence (p=0.001). In addition, patients with methylation of T-cadherin had worse overall survival (p=0.018) and progression-free survival (p<0.001) than patients without, and methylation of T-cadherin in sera was an independent prognostic factor for worse overall survival (HR: 3.626, 95% CI: 1.112–9.624, p=0.007) and progression-free survival (HR: 4.201, 95% CI: 1.562–10.038, p<0.001) of patients with OSCC. These results demonstrated that methylation of T-cadherin was frequently detected in sera of patients with OSCC, which was associated with risk factors of poor outcomes, and may act as a potential independent prognostic marker for patients with OSCC.