Prostanoid receptor genes confer poor prognosis in head and neck squamous cell carcinoma via epigenetic inactivation
Posted on 2020-01-23 - 04:59
Abstract Background Chronic inflammation is a risk factor for head and neck squamous cell carcinoma (HNSCC) and other diseases. Prostanoid receptors are clearly involved in the development of many types of cancer. However, their role is not simple and is poorly understood in HNSCC. Methods Methylation profiles of prostanoid receptor family genes were generated for tumour samples obtained from 274 patients with HNSCC, including 69 hypopharynx, 51 larynx, 79 oral cavity, and 75 oropharynx tumour samples, by quantitative methylation-specific PCR. Promoter methylation was then evaluated with respect to various clinical characteristics and patient survival. Results The mean number of methylated genes per sample was 2.05 ± 2.59 (range 0 to 9). Promoters of PTGDR1, PTGDR2, PTGER1, PTGER2, PTGER3, PTGER4, PTGFR, PTGIR, and TBXA2R were methylated in 43.8%, 18.2%, 25.5%, 17.5%, 41.2%, 8.0%, 19.3%, 20.4%, and 11.3% of the samples, respectively. Methylation indices for prostanoid receptor family genes tended to be higher as the number of TET methylation events increased. Patients with 5–9 methylated genes had a significantly lower survival rate than that of patients with 0–4 methylated genes (log-rank test, P= 0.007). In multivariate analyses, PTGDR1 methylation was most highly correlated with recurrence in patients with hypopharyngeal cancer (P = 0.014). A similar correlation was observed for PTGER4 in patients with laryngeal cancer (P = 0.046). Methylation of the PTGIR and TBXA2R promoters was positively correlated with recurrence in oropharyngeal cancer (P = 0.028 and P = 0.006, respectively). Moreover, Patients with 5–9 methylated genes were extremely lower of 5hmC levels (P = 0.035) and was correlated with increasing expression of DNMT3A and DNMT3B (P < 0.05 and P < 0.05, respectively). Conclusion We characterised the relationship between the methylation status of prostanoid receptor genes and recurrence in HNSCC. These results provide new perspectives for the development of molecular targeted treatment approaches.
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Misawa, Kiyoshi; Mima, Masato; Satoshi, Yamada; Imai, Atsushi; Mochizuki, Daiki; Ishikawa, Ryuji; et al. (2020). Prostanoid receptor genes confer poor prognosis in head and neck squamous cell carcinoma via epigenetic inactivation. figshare. Collection. https://doi.org/10.6084/m9.figshare.c.4827666.v1
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AUTHORS (11)
KM
Kiyoshi Misawa
MM
Masato Mima
YS
Yamada Satoshi
AI
Atsushi Imai
DM
Daiki Mochizuki
RI
Ryuji Ishikawa
JK
Junya Kita
YY
Yuki Yamaguchi
SE
Shiori Endo
YM
Yuki Misawa
HM
Hiroyuki Mineta