Open AccessEstablishment of epigenetic markers to predict irradiation efficacy against oropharyngeal cancer
Author(s) -
Kurokawa Tomoya,
Nakagawa Takuya,
Matsusaka Keisuke,
Fukuyo Masaki,
Mima Masato,
Misawa Kiyoshi,
Rahmutulla Bahityar,
Ikeda Junichiro,
Hanazawa Toyoyuki,
Okamoto Yoshitaka,
Kaneda Atsushi
Publication year - 2020
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.14338
Subject(s) - epigenetics , cancer , oncology , medicine , cancer research , biology , genetics , gene
Abstract Irradiation, or chemoradiotherapy, is a curative treatment for oropharyngeal squamous cell carcinoma (OPSCC). Its invasiveness, however, can often negate its efficacy. Therefore, developing methods to predict which patients would benefit from irradiation is urgent. Promoter DNA hypermethylation was recently reported to correlate with favorable OPSCC prognosis. It is still unclear, however, whether there is an association between promoter DNA methylation and response to irradiation. In this study, we analyzed DNA methylation in the specimens from 40 OPSCC patients who had undergone irradiation, using the Infinium assay. Our results showed significant correlation between high levels of promoter DNA methylation and better response to treatment ( P < 0.01). We used the 10 most differentially‐methylated genes between responders and non–responders to develop a panel of predictive markers for efficacy. Our panel had high sensitivity, specificity and accuracy (92%, 93% and 93%, respectively). We conducted pyrosequencing to quantitatively validate the methylation levels of 8 of the 10 marker genes ( ROBO1 , ULK4P3 , MYOD1 , LBX1 , CACNA1A , IRX4 , DPYSL3 and ELAVL2 ) obtained by Infinium. The validation by pyrosequencing showed that these 8 genes had a high prediction performance for the training set of 40 specimens and for a validation set of 35 OPSCC specimens, showing 96% sensitivity, 89% specificity and 94% accuracy. Methylation of these markers correlated significantly with better progression‐free and overall survival rates, regardless of human papillomavirus status. These results indicate that increased DNA methylation is associated with better responses to irradiation therapy and that DNA methylation can help establish efficacy prediction markers in OPSCC.