Sichuan Cancer Hospital and Institute, University of Electronic Science and Technology of China, Chengdu, China.
Department of Clinical Laboratory, The Third Affiliated Hospital of Guangzhou Medical University, Liwan, Guangzhou, China.
Neoplasma. 2021 May;68(3):528-534. doi: 10.4149/neo_2021_201110N1203. Epub 2021 Feb 11.
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.
T-钙黏蛋白作为一种抑癌基因，其在多种人类癌症中常因启动子异常甲基化而失活，但在口腔鳞状细胞癌（OSCC）中的甲基化状态研究甚少。因此，本研究旨在探讨 T-钙黏蛋白在 OSCC 患者血清中的甲基化状态的临床意义和预后价值。采用甲基化特异性 PCR（MSP）和亚硫酸氢盐测序 PCR（BSP）检测 T-钙黏蛋白的甲基化状态。然后，在 202 例 OSCC 患者和 68 例对照中，研究 T-钙黏蛋白甲基化状态与各种临床病理变量或患者生存的关系。在 202 例 OSCC 患者中，有 62 例（30.7%）检测到 T-钙黏蛋白甲基化，并用 BSP 验证了相应组织中 T-钙黏蛋白的甲基化状态。T-钙黏蛋白的甲基化与肿瘤 T 分期较晚（p<0.001）和 N 分期（p=0.003）、阳性淋巴结转移（p=0.004）和肿瘤复发（p=0.001）显著相关。此外，与无 T-钙黏蛋白甲基化的患者相比，有 T-钙黏蛋白甲基化的患者总生存（p=0.018）和无进展生存（p<0.001）更差，血清 T-钙黏蛋白的甲基化是总生存（HR：3.626，95%CI：1.112-9.624，p=0.007）和无进展生存（HR：4.201，95%CI：1.562-10.038，p<0.001）较差的独立预后因素。这些结果表明，T-钙黏蛋白在 OSCC 患者的血清中经常被检测到，与不良预后的危险因素相关，并且可能是 OSCC 患者的一个潜在的独立预后标志物。
