Kondo, Kazuya Tokushima University Tokushima University Educator and Researcher Directory KAKEN Search Researchers
Kohmoto, Tomohiro Tokushima University
Takizawa, Hiromitsu Tokushima University Tokushima University Educator and Researcher Directory KAKEN Search Researchers
Imoto, Issei Tokushima University|Aichi Cancer Center Research Institute|Nagoya University KAKEN Search Researchers
Tangoku, Akira Tokushima University Tokushima University Educator and Researcher Directory KAKEN Search Researchers
Thesis or Dissertation
Background and Objectives: In a previous genome-wide screening, we identified hypermethylated CpG islands around glutamate decarboxylase 1 (GAD1) in lung adenocarcinoma (LADC). In this study, we aimed to investigate the methylation and expression status of GAD1 and its prognostic value in patients with LADC.
Methods: GAD1 methylation and mRNA expression status were analyzed using 33 tumorous and paired non-tumorous LADC samples and publicly available datasets. The prognostic value of GAD1 overexpression was investigated using publicly available datasets of mRNA levels and 162 cases of LADC by immunohistochemistry.
Results: The methylation and mRNA expression levels of GAD1, each having a positive correlation, were significantly higher in LADC tumors than in paired non-tumorous tissues. LADC patients with higher GAD1 mRNA expression showed significantly poorer prognosis for overall survival in publicly available datasets. Higher immunoreactivity of GAD1 was significantly associated with the pathological stage, pleural invasion, lymph vessel invasion, and poorer prognosis for cancer-specific and disease-free survival. Multivariate analysis revealed that GAD1 protein overexpression is an independent prognosticator for disease-free survival.
Conclusions: GAD1 mRNA and protein expression levels were significant prognostic factors in LADC, suggesting that they might be useful biomarkers to stratify patients with worse clinical outcome after resection.
John Wiley & Sons, Ltd
© 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.( https://creativecommons.org/licenses/by/4.0/ )
|DOI (Published Version)|
|URL ( Publisher's Version )|
k3321_abstract_review.pdf 199 KB
k3321_fulltext.pdf 1010 KB
|MEXT report number||
Doctor of Medical Science