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ID 113692
Title Alternative
肺腺癌患者の予後予測におけるGAD1過剰発現の有用性
Author
Masuda, Kiyoshi Tokushima University|Kawasaki Medical School KAKEN Search Researchers
Kohmoto, Tomohiro Tokushima University
Imoto, Issei Tokushima University|Aichi Cancer Center Research Institute|Nagoya University Tokushima University Educator and Researcher Directory KAKEN Search Researchers
Keywords
GAD1
lung adenocarcinoma
expression
prognosis
DNA methylation
Content Type
Thesis or Dissertation
Description
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.
Journal Title
Cancer Medicine
ISSN
20457634
Publisher
John Wiley & Sons, Ltd
Volume
8
Issue
9
Start Page
4189
End Page
4199
Published Date
2019-06-17
Remark
内容要旨・審査要旨・論文本文の公開
本論文は,著者Mitsuhiro Tsuboiの学位論文として提出され,学位審査・授与の対象となっている。
Rights
© 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/ )
EDB ID
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
ETD
MEXT report number
甲第3321号
Diploma Number
甲医第1423号
Granted Date
2019-07-25
Degree Name
Doctor of Medical Science
Grantor
Tokushima University
departments
University Hospital
Medical Sciences