G Protein-Coupled Receptor Genes, PTGDR1, PTGDR2, and PTGIR, Are Candidate Epigenetic Biomarkers and Predictors for Treated Patients with HPV-Associated Oropharyngeal Cancer.

G Protein-Coupled Receptor Genes, PTGDR1, PTGDR2, and PTGIR, Are Candidate Epigenetic Biomarkers and Predictors for Treated Patients with HPV-Associated Oropharyngeal Cancer.
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G蛋白偶联受体基因PTGDR1、PTGDR2和PTGIR是HPV相关口咽癌患者的候选表观遗传生物标记物和预测因子

DOI:
10.3390/microorganisms8101504
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发表时间:
2020-09-29
期刊:
影响因子:
4.5
通讯作者:
Mineta H
Mineta H
中科院分区:
生物学3区
文献类型:
--
作者:
Misawa K;Imai A;Kanazawa T;Mima M;Yamada S;Mochizuki D;Yamada T;Shinmura D;Ishikawa R;Kita J;Yamaguchi Y;Misawa Y;Mineta H

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人乳头瘤病毒(HPV)相关口咽癌(OPCs)和HPV阴性口咽癌的生物学差异可能对患者管理有影响。早期发现对于降低hpv相关的OPC死亡率至关重要。循环肿瘤DNA (ctDNA)可以作为监测临床相关癌症遗传和表观遗传修饰的生物标志物。我们利用定量甲基化特异性聚合酶链反应(Q-MSP)分析了验证(85个OPC初级样本)和验证(8个OPC ctDNA样本)中24个G蛋白偶联受体(GPCR)基因的甲基化状态。基于q - msp的85例OPC初级样本验证研究显示,在OPC和hpv相关OPC的高甲基化组(≥14个甲基化基因)中,GPCR基因与复发显著相关(p < 0.001)。在Kaplan-Meier估计和多变量Cox比例风险分析中,13个GPCR基因与甲基化组复发率增加显著相关。此外,ctDNA的验证研究表明,其中三个基因(前列腺素D2受体1:PTGDR1,前列腺素D2受体2:PTGDR2和前列腺素I2受体:PTGIR)作为新兴生物标志物具有预测性能。我们鉴定了GPCR基因甲基化状态与hpv相关OPC预后之间的关系。我们的研究结果强调了ctDNA甲基化检测在hpv相关OPC临床管理中的潜在效用。
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 (p < 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: PTGDR1, Prostaglandin D2 receptor 2: PTGDR2, and Prostaglandin I2 Receptor: PTGIR) 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.
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