High-risk HPV infection-associated hypermethylated genes in oropharyngeal squamous cell carcinomas

High-risk HPV infection-associated hypermethylated genes in oropharyngeal squamous cell carcinomas

Background HPV-positive oropharyngeal squamous cell carcinomas (OPSCCs) are sensitive to chemo-radiation therapy and have favorable survival outcomes compared with HPV-negative cancers. These tumors are usually not related to tobacco and alcohol exposure. Therefore, diagnosing HPV-positive OPSCCs fo...

Full description

Saved in:
Bibliographic Details
Published in:BMC cancer Vol. 22; no. 1; pp. 1 - 1146
Main Authors: Inokawa, Yoshikuni, Hayashi, Masamichi, Begum, Shahnaz, Noordhuis, Maartje G, Sidransky, Daivd, Califano, Joseph, Koch, Wayne, Brait, Mariana, Westra, William H, Hoque, Mohammad O
Format: Journal Article
Language:English
Published: London BioMed Central Ltd 07-11-2022
BioMed Central
BMC
Subjects:
AGTR1
Alcohol
Analysis
Cancer
Care and treatment
Cell cycle
Complications and side effects
DNA methylation
Epigenetic inheritance
Epigenetics
Gene mutations
Genes
Genetic aspects
Genetic testing
Health aspects
HPV
Human papillomavirus
Infections
Labeling
Malignancy
Medical prognosis
Methylation
Monoclonal antibodies
Oropharyngeal SCC
Oropharyngolaryngeal carcinoma
Papillomavirus infections
Patient outcomes
Phenotypes
Prevention
Radiation therapy
Radiotherapy
Risk factors
Squamous cell carcinoma
Throat cancer
Tissue inhibitor of metalloproteinase 3
Tumors
United States
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Background HPV-positive oropharyngeal squamous cell carcinomas (OPSCCs) are sensitive to chemo-radiation therapy and have favorable survival outcomes compared with HPV-negative cancers. These tumors are usually not related to tobacco and alcohol exposure. Therefore, diagnosing HPV-positive OPSCCs for the appropriate disease management is crucial, and no suitable markers are available for detecting early malignancies in HPV-infected tissues. In this study, we attempt to find HPV-specific epigenetic biomarkers for OPSCCs. Methods A total of 127 surgical samples were analyzed for HPV positivity and promoter methylation of a panel of genes. HPV detection was performed by PCR detection of HPV E6 and E7 viral oncoproteins. In addition, promoter methylation of a total of 8 genes (DAPK, FHIT, RASSF1A, TIMP3, AGTR1, CSGALNACT2, GULP1 and VGF) was analyzed by quantitative-methylation specific PCR (QMSP), and their associations with HPV positivity or RB/p16 expressions were evaluated. Results AGTR1 and FHIT were frequently methylated in HPV-positive OPSCC samples with a good area under the curve (AUC over 0.70). In addition, these genes' promoter methylation was significantly associated with p16 positive and RB negative cases, which were the characteristics of OPSCC cases with favorable survival outcomes. Either AGTR1 or FHIT methylated cases were significantly associated with HPV-positive cancers with 92.0% sensitivity (P < 0.001). Also, they had significantly better overall survival (P = 0.047) than both unmethylated cases. Conclusions A combination of AGTR1 and FHIT methylation demonstrated a suitable detection marker of OPSCCs derived from the HPV-infected field, familiar with p16-positive and RB-negative phenotypes. Keywords: HPV, Oropharyngeal SCC, Methylation, AGTR1
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:1471-2407
1471-2407
DOI:10.1186/s12885-022-10227-w