Evaluation of epigenetic inactivation of vascular endothelial growth factor receptors in head and neck squamous cell carcinoma
The aim of this study was to determine the methylation status of the genes encoding the vascular endothelial growth factor receptors and to evaluate the usefulness of VEGFR methylation as a prognostic indicator in head and neck squamous cell carcinoma. VEGFR messenger RNA expression and promoter met...
Saved in:
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
SAGE Publishing
2017-07-01
|
| Series: | Tumor Biology |
| Online Access: | https://doi.org/10.1177/1010428317711657 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849697675986862080 |
|---|---|
| author | Yuki Misawa Kiyoshi Misawa Hideya Kawasaki Atsushi Imai Daiki Mochizuki Ryuji Ishikawa Shiori Endo Masato Mima Takeharu Kanazawa Toshihide Iwashita Hiroyuki Mineta |
| author_facet | Yuki Misawa Kiyoshi Misawa Hideya Kawasaki Atsushi Imai Daiki Mochizuki Ryuji Ishikawa Shiori Endo Masato Mima Takeharu Kanazawa Toshihide Iwashita Hiroyuki Mineta |
| author_sort | Yuki Misawa |
| collection | DOAJ |
| description | The aim of this study was to determine the methylation status of the genes encoding the vascular endothelial growth factor receptors and to evaluate the usefulness of VEGFR methylation as a prognostic indicator in head and neck squamous cell carcinoma. VEGFR messenger RNA expression and promoter methylation were examined in a panel of cell lines via quantitative reverse transcription and methylation-specific polymerase chain reaction, respectively. Promoter methylation was compared with clinical characteristics in 128 head and neck squamous cell carcinoma samples. The normalized methylation values for the VEGFR1, VEGFR2 and VEGFR3 promoters tended to be higher in the tumour cell lines than in normal tonsil samples, whereas amounts of VEGFR1, VEGFR2 and VEGFR3 messenger RNA were significantly higher. Methylation of the VEGFR1 promoter (p = 0.003; 66/128 head and neck squamous cell carcinoma samples, 52%) and VEGFR3 promoter (p = 0.043; 53/128 head and neck squamous cell carcinoma samples, 41%) significantly correlated with recurrence, whereas methylation of the VEGFR2 promoter significantly correlated with lymph node metastasis (p = 0.046; 47/128 head and neck squamous cell carcinoma samples, 37%). Concurrent methylation of the VEGFR1 and VEGFR3 promoters significantly correlated with reduced disease-free survival (log-rank test, p = 0.009). In a multivariate logistic regression analysis, methylation of the VEGFR1, VEGFR3 and both the VEGFR1 and VEGFR3 promoters independently predicted recurrence (odds ratios and 95% confidence intervals: 3.19, 1.51–6.75 (p = 0.002); 2.24, 1.06–4.76 (p = 0.035); and 2.56, 1.09–6.05 (p = 0.032), respectively). Methylation of the VEGFR promoters predicts poor prognosis in head and neck squamous cell carcinoma patients. |
| format | Article |
| id | doaj-art-e9601ec0ddb64382abd55826c7aa383e |
| institution | DOAJ |
| issn | 1423-0380 |
| language | English |
| publishDate | 2017-07-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Tumor Biology |
| spelling | doaj-art-e9601ec0ddb64382abd55826c7aa383e2025-08-20T03:19:10ZengSAGE PublishingTumor Biology1423-03802017-07-013910.1177/1010428317711657Evaluation of epigenetic inactivation of vascular endothelial growth factor receptors in head and neck squamous cell carcinomaYuki Misawa0Kiyoshi Misawa1Hideya Kawasaki2Atsushi Imai3Daiki Mochizuki4Ryuji Ishikawa5Shiori Endo6Masato Mima7Takeharu Kanazawa8Toshihide Iwashita9Hiroyuki Mineta10Department of Otorhinolaryngology/Head and Neck Surgery, Hamamatsu University School of Medicine, Hamamatsu, JapanDepartment of Otorhinolaryngology/Head and Neck Surgery, Hamamatsu University School of Medicine, Hamamatsu, JapanDepartment of Regenerative and Infectious Pathology, Hamamatsu University School of Medicine, Hamamatsu, JapanDepartment of Otorhinolaryngology/Head and Neck Surgery, Hamamatsu University School of Medicine, Hamamatsu, JapanDepartment of Otorhinolaryngology/Head and Neck Surgery, Hamamatsu University School of Medicine, Hamamatsu, JapanDepartment of Otorhinolaryngology/Head and Neck Surgery, Hamamatsu University School of Medicine, Hamamatsu, JapanDepartment of Otorhinolaryngology/Head and Neck Surgery, Hamamatsu University School of Medicine, Hamamatsu, JapanDepartment of Otorhinolaryngology/Head and Neck Surgery, Hamamatsu University School of Medicine, Hamamatsu, JapanDepartment of Otolaryngology – Head and Neck Surgery, Jichi Medical University, Shimotsuke, JapanDepartment of Regenerative and Infectious Pathology, Hamamatsu University School of Medicine, Hamamatsu, JapanDepartment of Otorhinolaryngology/Head and Neck Surgery, Hamamatsu University School of Medicine, Hamamatsu, JapanThe aim of this study was to determine the methylation status of the genes encoding the vascular endothelial growth factor receptors and to evaluate the usefulness of VEGFR methylation as a prognostic indicator in head and neck squamous cell carcinoma. VEGFR messenger RNA expression and promoter methylation were examined in a panel of cell lines via quantitative reverse transcription and methylation-specific polymerase chain reaction, respectively. Promoter methylation was compared with clinical characteristics in 128 head and neck squamous cell carcinoma samples. The normalized methylation values for the VEGFR1, VEGFR2 and VEGFR3 promoters tended to be higher in the tumour cell lines than in normal tonsil samples, whereas amounts of VEGFR1, VEGFR2 and VEGFR3 messenger RNA were significantly higher. Methylation of the VEGFR1 promoter (p = 0.003; 66/128 head and neck squamous cell carcinoma samples, 52%) and VEGFR3 promoter (p = 0.043; 53/128 head and neck squamous cell carcinoma samples, 41%) significantly correlated with recurrence, whereas methylation of the VEGFR2 promoter significantly correlated with lymph node metastasis (p = 0.046; 47/128 head and neck squamous cell carcinoma samples, 37%). Concurrent methylation of the VEGFR1 and VEGFR3 promoters significantly correlated with reduced disease-free survival (log-rank test, p = 0.009). In a multivariate logistic regression analysis, methylation of the VEGFR1, VEGFR3 and both the VEGFR1 and VEGFR3 promoters independently predicted recurrence (odds ratios and 95% confidence intervals: 3.19, 1.51–6.75 (p = 0.002); 2.24, 1.06–4.76 (p = 0.035); and 2.56, 1.09–6.05 (p = 0.032), respectively). Methylation of the VEGFR promoters predicts poor prognosis in head and neck squamous cell carcinoma patients.https://doi.org/10.1177/1010428317711657 |
| spellingShingle | Yuki Misawa Kiyoshi Misawa Hideya Kawasaki Atsushi Imai Daiki Mochizuki Ryuji Ishikawa Shiori Endo Masato Mima Takeharu Kanazawa Toshihide Iwashita Hiroyuki Mineta Evaluation of epigenetic inactivation of vascular endothelial growth factor receptors in head and neck squamous cell carcinoma Tumor Biology |
| title | Evaluation of epigenetic inactivation of vascular endothelial growth factor receptors in head and neck squamous cell carcinoma |
| title_full | Evaluation of epigenetic inactivation of vascular endothelial growth factor receptors in head and neck squamous cell carcinoma |
| title_fullStr | Evaluation of epigenetic inactivation of vascular endothelial growth factor receptors in head and neck squamous cell carcinoma |
| title_full_unstemmed | Evaluation of epigenetic inactivation of vascular endothelial growth factor receptors in head and neck squamous cell carcinoma |
| title_short | Evaluation of epigenetic inactivation of vascular endothelial growth factor receptors in head and neck squamous cell carcinoma |
| title_sort | evaluation of epigenetic inactivation of vascular endothelial growth factor receptors in head and neck squamous cell carcinoma |
| url | https://doi.org/10.1177/1010428317711657 |
| work_keys_str_mv | AT yukimisawa evaluationofepigeneticinactivationofvascularendothelialgrowthfactorreceptorsinheadandnecksquamouscellcarcinoma AT kiyoshimisawa evaluationofepigeneticinactivationofvascularendothelialgrowthfactorreceptorsinheadandnecksquamouscellcarcinoma AT hideyakawasaki evaluationofepigeneticinactivationofvascularendothelialgrowthfactorreceptorsinheadandnecksquamouscellcarcinoma AT atsushiimai evaluationofepigeneticinactivationofvascularendothelialgrowthfactorreceptorsinheadandnecksquamouscellcarcinoma AT daikimochizuki evaluationofepigeneticinactivationofvascularendothelialgrowthfactorreceptorsinheadandnecksquamouscellcarcinoma AT ryujiishikawa evaluationofepigeneticinactivationofvascularendothelialgrowthfactorreceptorsinheadandnecksquamouscellcarcinoma AT shioriendo evaluationofepigeneticinactivationofvascularendothelialgrowthfactorreceptorsinheadandnecksquamouscellcarcinoma AT masatomima evaluationofepigeneticinactivationofvascularendothelialgrowthfactorreceptorsinheadandnecksquamouscellcarcinoma AT takeharukanazawa evaluationofepigeneticinactivationofvascularendothelialgrowthfactorreceptorsinheadandnecksquamouscellcarcinoma AT toshihideiwashita evaluationofepigeneticinactivationofvascularendothelialgrowthfactorreceptorsinheadandnecksquamouscellcarcinoma AT hiroyukimineta evaluationofepigeneticinactivationofvascularendothelialgrowthfactorreceptorsinheadandnecksquamouscellcarcinoma |