Stratification of HPV-associated and HPV-negative oropharyngeal squamous cell carcinomas based on DNA methylation epigenotypes.
Biomarkers, Tumor
/ genetics
Carcinoma, Squamous Cell
/ classification
Case-Control Studies
DNA Methylation
Epigenesis, Genetic
Follow-Up Studies
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Humans
Oropharyngeal Neoplasms
/ classification
Papillomaviridae
/ pathogenicity
Papillomavirus Infections
/ complications
Prognosis
Survival Rate
DNA methylation
head and neck squamous cell cancer
human papillomavirus
Journal
International journal of cancer
ISSN: 1097-0215
Titre abrégé: Int J Cancer
Pays: United States
ID NLM: 0042124
Informations de publication
Date de publication:
01 05 2020
01 05 2020
Historique:
received:
12
11
2019
revised:
25
12
2019
accepted:
15
01
2020
pubmed:
31
1
2020
medline:
1
7
2020
entrez:
31
1
2020
Statut:
ppublish
Résumé
While the incidence of oropharyngeal squamous cell carcinoma (OPSCC) has been increasing in these two decades, primarily due to human papillomavirus (HPV), stratification of OPSCC into molecular subgroups showing different clinicopathological features has not been fully investigated. We performed DNA methylome analysis using Infinium 450k for 170 OPSCC cases, including 89 cases in our cohort and 81 cases reported by The Cancer Genome Atlas, together with targeted exon sequencing analysis. We stratified OPSCC by hierarchical clustering analysis using methylome data. Methylation levels of classifier markers were validated quantitatively using pyrosequencing, and area under the curve (AUC) values of receiver operating characteristics (ROC) curves were calculated. OPSCC was stratified into four epigenotypes: HPV(+) high-methylation (OP1), HPV(+) intermediate-methylation (OP2), HPV(-) intermediate-methylation (OP3) and HPV(-) low-methylation (OP4). Ten methylation marker genes were generated: five to classify HPV(+) cases into OP1 and OP2, and five to classify HPV(-) cases into OP3 and OP4. AUC values of ROC curves were 0.969 and 0.952 for the two marker panels, respectively. While significantly higher TP53 mutation and CCND1 copy number gains were observed in HPV(-) than in HPV(+) groups (p < 0.01), no significant difference of genomic aberrations was observed between OP1 and OP2, or OP3 and OP4. The four epigenotypes showed significantly different prognosis (p = 0.0006), distinguishing the most favorable OPSCC subgroup (OP1) among generally favorable HPV(+) cases, and the most unfavorable OPSCC subgroup (OP3) among generally unfavorable HPV(-) cases. HPV(+) and HPV(-) OPSCC are further divided into distinct DNA methylation epigenotypes, showing significantly different prognosis.
Substances chimiques
Biomarkers, Tumor
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2460-2474Informations de copyright
© 2020 UICC.
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