Establishment of epigenetic markers to predict irradiation efficacy against oropharyngeal cancer

Tomoya Kurokawa, Takuya Nakagawa, Keisuke Matsusaka, Masaki Fukuyo, Masato Mima, Kiyoshi Misawa, Bahityar Rahmutulla, Jun-ichiro Ikeda, Toyoyuki Hanazawa, Yoshitaka Okamoto, Atsushi Kaneda
2020 Cancer Science  
Irradiation, or chemoradiotherapy, is curative treatment for oropharyngeal squamous cell carcinoma (OPSCC). Its invasiveness, however, can often overwhelm its efficacy. It is therefore urgent issue to develop methods to predict which patients would benefit from irradiation. Promoter DNA hypermethylation was recently reported to correlate with favorable OPSCC prognosis. It is still unclear, however, whether there is association between promoter DNA methylation and response to irradiation. In
more » ... 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%, 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.
doi:10.1111/cas.14338 pmid:32012407 fatcat:bsrrsadfpzhepfldqliiqurleu