Novel prognostic value and potential utility of opioid receptor gene methylation in liquid biopsy for oral cavity cancer
Novel prognostic value and potential utility of opioid receptor gene methylation in liquid biopsy for oral cavity cancer
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DOI：
10.1016/j.currproblcancer.2021.100834
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发表时间：
2022-03-17
影响因子：
2.6
通讯作者：
Misawa, Kiyoshi
中科院分区：
文献类型：
--
作者：
Ishikawa, Ryuji;Imai, Atsushi;Misawa, Kiyoshi
阿片类药物是一类与G蛋白偶联受体（称为阿片受体（OR））结合的娱乐性药物和处方药。OR参与许多类型癌症的发展;然而，它们在头颈部鳞状细胞癌（HNSCC）中的作用是复杂的，并且知之甚少。在这里，我们使用定量甲基化特异性PCR（Q-MSP）分析了验证（301例HNSCC原始样本）和验证（5例循环肿瘤DNA [ctDNA]样本）研究中5个OR基因的甲基化状态。OPRL 1和OPRM 1甲基化水平在HNSCC组织中显著高于来自相同个体的相应正常组织（分别为P = 0.001和P < 0.001）。在Kaplan-Meier估计和多变量考克斯比例风险分析中，两个基因（OPRL 1和OPRM 1）与口腔癌甲基化组的复发率增加显著相关。此外，ctDNA的验证研究表明，OPRL 1基因表现出作为新兴生物标志物的预测性能，并且每个基因都能够区分血浆和无肿瘤个体。我们描述了OR基因甲基化状态与口腔癌预后之间的关系。我们的研究结果突出了基于ctDNA甲基化的检测在口腔癌临床管理中的潜在效用。(c)2021爱思唯尔公司All rights reserved.
Opioids are a class of recreational drugs and prescription medications that bind to a group of G-protein coupled receptors known as opioid receptors (ORs). ORs are involved in the development of many types of cancer; however, their role in head and neck squamous cell carcinoma (HNSCC) is complex and poorly understood. Here, we analyzed the methylation status of five OR genes in verification (301 HNSCC primary samples) and validation (five circulating tumor DNA [ctDNA] samples) studies using quantitative methylation-specific PCR (Q-MSP). OPRL1 and OPRM1 methylation levels were significantly higher in HNSCC tissues than in corresponding normal tissues from the same individuals ( P = 0.001 and P < 0.001, respectively). In Kaplan-Meier estimate and multivariate Cox proportional hazard analyses, two genes (OPRL1 and OPRM1) were significantly associated with increased recurrence in the methylation group with oral cavity cancer. Furthermore, a validation study of ctDNA demonstrated that OPRL1 genes exhibited predictive performance as emerging biomarkers and were each capable of discriminating the plasma from tumor-free individuals. We characterized the relationship between OR gene methylation status and outcomes in oral cavity cancer. Our results highlight the potential utility of ctDNA methylation-based detection in the clinical management of oral cavity cancer. (c) 2021 Elsevier Inc. All rights reserved.