Misawa Kiyoshi, Imai Atsushi, Kanazawa Takeharu, Mima Masato, Yamada Satoshi, Mochizuki Daiki, Yamada Taiki, Shinmura Daichi, Ishikawa Ryuji, Kita Jyunya, Yamaguchi Yuki, Misawa Yuki, Mineta Hiroyuki
Department of Otolaryngology/Head and Neck Surgery, Hamamatsu University School of Medicine, Hamamatsu 431-3192, Japan.
Department of Otorhinolaryngology/Head and Neck Surgery, Jichi Medical University, Shimotsuke, Tochigi 329-0498, Japan.
Microorganisms. 2020 Sep 29;8(10):1504. doi: 10.3390/microorganisms8101504.
Differences in the biology of human papillomavirus (HPV)-associated oropharyngeal cancers (OPCs) and HPV-negative OPCs may have implications in patient management. Early detection is imperative to reduce HPV-associated OPC mortality. Circulating tumor DNA (ctDNA) can potentially serve as a biomarker for monitoring clinically relevant cancer-related genetic and epigenetic modifications. We analyzed the methylation status of 24 G protein-coupled receptor (GPCR) genes in verification (85 OPC primary samples) and validation (8 OPC ctDNA samples) studies using quantitative methylation-specific polymerase chain reaction (Q-MSP). The Q-MSP-based verification study with 85 OPC primary samples revealed the GPCR genes that were significantly associated with recurrence in high methylation groups (≥14 methylated genes) with OPC and HPV-associated OPC ( < 0.001). In the Kaplan-Meier estimate and multivariate Cox proportional hazard analyses, 13 GPCR genes were significantly related to increased recurrence in the methylation group. Furthermore, the validation study on ctDNA showed that three of these genes (Prostaglandin D2 receptor 1: , Prostaglandin D2 receptor 2: , and Prostaglandin I2 Receptor: ) had a prediction performance as emerging biomarkers. We characterized the relationship between the methylation status of GPCR genes and outcomes in HPV-associated OPC. Our results highlight the potential utility of ctDNA methylation-based detection for the clinical management of HPV-associated OPC.
人乳头瘤病毒（HPV）相关的口咽癌（OPC）与HPV阴性的OPC在生物学特性上的差异可能对患者管理有影响。早期检测对于降低HPV相关OPC的死亡率至关重要。循环肿瘤DNA（ctDNA）有可能作为一种生物标志物，用于监测临床上相关的癌症相关基因和表观遗传修饰。我们在验证研究（85份OPC原发样本）和验证研究（8份OPC的ctDNA样本）中，使用定量甲基化特异性聚合酶链反应（Q-MSP）分析了24个G蛋白偶联受体（GPCR）基因的甲基化状态。基于Q-MSP的对85份OPC原发样本的验证研究揭示了在高甲基化组（≥14个甲基化基因）中与OPC和HPV相关OPC复发显著相关的GPCR基因（<0.001）。在Kaplan-Meier估计和多变量Cox比例风险分析中，13个GPCR基因与甲基化组中复发增加显著相关。此外，对ctDNA的验证研究表明，其中三个基因（前列腺素D2受体1： ，前列腺素D2受体2： ，以及前列腺素I2受体： ）具有作为新兴生物标志物的预测性能。我们描述了GPCR基因甲基化状态与HPV相关OPC预后之间的关系。我们的结果突出了基于ctDNA甲基化检测在HPV相关OPC临床管理中的潜在效用。
