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

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.

Epigenome-wide association study and epigenetic age acceleration associated with cigarette smoking among Costa Rican adults

“…MAPK4 is an atypical kinase involved with the AKT/mTOR signaling pathway, and overexpression is associated with acute lung injury and cancers 63 , 64 . Similarly, the HNRNPM and PTGIR proteins have been shown to promote cancerous cell growth and be associated with poorer oncogenic outcomes 65 , 66 . The latter is also involved with vascular remodeling, and its loss of function may increase risk for vessel stenosis and dissection 67 .…”

Immune Biomarkers in Blood from Sarcoma Patients: A Pilot Study

“…Ectopic expression of GATA3 in Th1 cells may also explain the failure to restore Th1 differentiation, thus reducing Th1 immune response in sarcomas. The PTGDR2 , a chemoattractant receptor molecule (CRTH2) , and CCR3 , are reported to be expressed on Th2 cells and eosinophils [ 50 , 51 ], and their co-expression was linked to Th2 response in sepsis inflammatory response [ 50 ]. The HOXA10 gene, which is expressed on human progenitor CD34 + cells [ 52 ], is reported to be lower in mature PBLs [ 53 ].…”

Methylation analysis of DCC gene in saliva samples is an efficient method for non-invasive detection of superficial hypopharyngeal cancer

“…As candidate genes for the detection of hypopharyngeal cancer, we selected genes that were previously reported by comprehensive analyses [ 23 , 24 ] and systematic reviews [ 25 , 26 ] as being hypermethylated in tissue or saliva samples in advanced HNSCC cases. Four genes, Deleted in Colorectal Cancer ( DCC ) [ 21 , 27 ], Prostaglandin D2 Receptor 1 ( PTGDR1 ) [ 28 , 29 ], Endothelin Receptor β ( EDNRB ) [ 21 , 30 ], and E Cadherin ( ECAD ) [ 31 , 32 ], were selected for this study. Primers were designed to specifically amplify the bisulfite-converted DNA of each gene.…”