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

Kiyoshi Misawa,Atsushi Imai,Yuki Misawa,Jyunya Kita,Takeharu Kanazawa,Satoshi Yamada,Masato Mima,Daiki Mochizuki,Daichi Shinmura,Hiroyuki Mineta,Taiki Yamada,Ryuji Ishikawa,Yuki Yamaguchi

doi:10.3390/microorganisms8101504

Kiyoshi Misawa, Atsushi Imai + Show 11 more

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https://doi.org/10.3390/microorganisms8101504

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Journal: Microorganisms	Publication Date: Sep 29, 2020
Citations: 10	License type: CC BY 4.0

Affiliation: Hamamatsu University School of Medicine

Abstract

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.

Highlights

G protein-coupled receptors (GPCRs) are the largest class of cell-surface receptors involved in several cancers, including head and neck squamous cell carcinoma (HNSCC) [1]
Studies have revealed the aberrant expression of GPCRs in human cancers in response to unfavorable events such as gene point mutations, changes in gene copy number, and gene silencing via epigenetic modifications [2]
Considering the mean methylation index values, no significant association was observed between human papillomavirus (HPV)-associated oropharyngeal cancers (OPCs) and HPV-negative OPC groups (Figure 1C)

Summary

Introduction

G protein-coupled receptors (GPCRs) are the largest class of cell-surface receptors involved in several cancers, including head and neck squamous cell carcinoma (HNSCC) [1]. Detection of aberrant circulating tumor DNA (ctDNA) specific for GPCRs may potentially serve as a minimally invasive monitoring strategy for the early detection of tumor recurrence. Some clinicopathological parameters, including primary site, nodal involvement, tumor thickness, and status of surgical margins, have been associated with prognosis [5]. Current diagnostic strategies for post-treatment surveillance of patients with HNSCC involve monitoring by clinical evaluation in combination with flexible endoscopy and conventional imaging [6]. CtDNA may potentially be used to monitor early disease relapse and offer a dynamic molecular reflection of genomic alterations in cancer Advances in genomic technology have provided vast information on different cancer subtypes and introduced new therapeutic targets [7]. ctDNA may potentially be used to monitor early disease relapse and offer a dynamic molecular reflection of genomic alterations in cancer

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