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ID 114707
タイトル別表記
Claudin-6は、腸型胃がんの亜群において独立した予後因子であるとともにがん促進遺伝子として機能する
著者
河本, 知大 徳島大学大学院医科学教育部(医学専攻)
Shoda, Katsutoshi Kyoto Prefectural University of Medicine
Takahashi, Rizu Tokushima University
Ujiro, Sae Tokushima University
Ichikawa, Daisuke University of Yamanashi
Otsuji, Eigo Kyoto Prefectural University of Medicine
井本, 逸勢 Tokushima University|Aichi Cancer Center Research Institute|Nagoya University KAKEN研究者をさがす
キーワード
Claudin-6
Stomach
Neoplasms
Prognosis
Computer-simulation
Oncogenes
Stomach neoplasms
資料タイプ
学位論文
抄録
Background
We aimed to identify novel tumor-promoting drivers highly expressed in gastric cancer (GC) that contribute to worsened prognosis in affected patients.
Methods
Genes whose expression was increased and correlated with worse prognosis in GC were screened using datasets from the Cancer Genome Atlas and Gene Expression Omnibus. We examined Claudin-6 (CLDN6) immunoreactivity in GC tissues and the effect of CLDN6 on cellular functions in GC cell lines. The mechanisms underlying GC-promoting function of CLDN6 were also investigated.
Results
CLDN6 was identified as a gene overexpressed in GC tumors as compared with adjacent non-tumorous tissues and whose increased expression was positively correlated with worse overall survival of GC patients, particularly those with Lauren’s intestinal type GC, in data from multiple publicly available datasets. Additionally, membranous CLDN6 immunoreactivity detected in intestinal type GC tumors was correlated with worse overall survival. In CLDN6-expressing GC cells, silencing of CLDN6 inhibited cell proliferation and migration/invasion abilities, possibly via suppressing transcription of YAP1 and its downstream transcriptional targets at least in part.
Conclusions:
This study identified CLDN6 as a GC-promoting gene, suggesting that CLDN6 to be a possible single prognostic marker and promising therapeutic target for a subset of GC patients.
掲載誌名
Gastric Cancer
ISSN
14363305
14363291
cat書誌ID
AA11316227
出版者
The International Gastric Cancer Association|The Japanese Gastric Cancer Association|Springer naure
23
3
開始ページ
403
終了ページ
417
発行日
2019-10-25
備考
内容要旨・審査要旨・論文本文の公開
本論文は,著者Tomohiro Kohmoto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。
This is a post-peer-review, pre-copyedit version of an article published in Gastric Cancer.
The final authenticated version is available online at: https://doi.org/10.1007/s10120-019-01014-x
出版社版DOI
出版社版URL
フルテキストファイル
言語
eng
著者版フラグ
博士論文全文を含む
文科省報告番号
甲第3356号
学位記番号
甲医第1439号
学位授与年月日
2020-03-23
学位名
博士(医学)
学位授与機関
徳島大学
部局
医学系