Altered Expression of Hippo Signaling Pathway Molecules in Intrahepatic Cholangiocarcinoma

Keishi Sugimachi, Miki Nishio, Shinichi Aishima, Yohsuke Kuroda, Tomohiro Iguchi, Hisateru Komatsu, Hidenari Hirata, Shotaro Sakimura, Hidetoshi Eguchi, Yuki Bekki, Kenji Takenaka, Yoshihiko Maehara, Akira Suzuki, Koshi Mimori

研究成果: ジャーナルへの寄稿記事

3 引用 (Scopus)

抄録

Objective: MOB1, a core component of the Hippo signaling pathway, suppresses cell proliferation, and MOB1 liver conditional knockout mice develop intrahepatic cholangiocarcinoma (ICC). However, its clinical significance in human ICC has not been established. The aim of this study was to characterize protein levels and the role of Hippo and TGF pathways in ICCs. Methods: The protein levels of yes-associated protein 1 (YAP1), MOB1, Smad2, and TGFβ2 in 88 ICC cases were analyzed. Protein level was graded by a scoring system; then, the clinicopathological factors, including prognosis, were analyzed based on protein level. Results: Nuclear overexpression of YAP1 was seen in 28 cases (31.8%), and it was significantly associated with a poor overall survival rate (p = 0.01). MOB1 expression decreased in 42 cases (47.7%) and was associated with a poor overall survival rate (p = 0.02). SMAD2 nuclear localization was significantly correlated with a high YAP1 level independent of TGFβ2. Multivariate analysis revealed that a high YAP1 level, a low MOB1 level, and lymphatic permeation were independent risk factors for overall survival. Conclusions: These results showed that key components of the Hippo signaling pathway are aberrantly expressed and associated with the malignant potential of human ICC.

元の言語英語
ページ(範囲)67-74
ページ数8
ジャーナルOncology (Switzerland)
93
発行部数1
DOI
出版物ステータス出版済み - 7 1 2017

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Cholangiocarcinoma
Proteins
Knockout Mice
Multivariate Analysis
Cell Proliferation
Survival
Liver

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

これを引用

Altered Expression of Hippo Signaling Pathway Molecules in Intrahepatic Cholangiocarcinoma. / Sugimachi, Keishi; Nishio, Miki; Aishima, Shinichi; Kuroda, Yohsuke; Iguchi, Tomohiro; Komatsu, Hisateru; Hirata, Hidenari; Sakimura, Shotaro; Eguchi, Hidetoshi; Bekki, Yuki; Takenaka, Kenji; Maehara, Yoshihiko; Suzuki, Akira; Mimori, Koshi.

:: Oncology (Switzerland), 巻 93, 番号 1, 01.07.2017, p. 67-74.

研究成果: ジャーナルへの寄稿記事

Sugimachi, K, Nishio, M, Aishima, S, Kuroda, Y, Iguchi, T, Komatsu, H, Hirata, H, Sakimura, S, Eguchi, H, Bekki, Y, Takenaka, K, Maehara, Y, Suzuki, A & Mimori, K 2017, 'Altered Expression of Hippo Signaling Pathway Molecules in Intrahepatic Cholangiocarcinoma', Oncology (Switzerland), 巻. 93, 番号 1, pp. 67-74. https://doi.org/10.1159/000463390
Sugimachi K, Nishio M, Aishima S, Kuroda Y, Iguchi T, Komatsu H その他. Altered Expression of Hippo Signaling Pathway Molecules in Intrahepatic Cholangiocarcinoma. Oncology (Switzerland). 2017 7 1;93(1):67-74. https://doi.org/10.1159/000463390
Sugimachi, Keishi ; Nishio, Miki ; Aishima, Shinichi ; Kuroda, Yohsuke ; Iguchi, Tomohiro ; Komatsu, Hisateru ; Hirata, Hidenari ; Sakimura, Shotaro ; Eguchi, Hidetoshi ; Bekki, Yuki ; Takenaka, Kenji ; Maehara, Yoshihiko ; Suzuki, Akira ; Mimori, Koshi. / Altered Expression of Hippo Signaling Pathway Molecules in Intrahepatic Cholangiocarcinoma. :: Oncology (Switzerland). 2017 ; 巻 93, 番号 1. pp. 67-74.
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abstract = "Objective: MOB1, a core component of the Hippo signaling pathway, suppresses cell proliferation, and MOB1 liver conditional knockout mice develop intrahepatic cholangiocarcinoma (ICC). However, its clinical significance in human ICC has not been established. The aim of this study was to characterize protein levels and the role of Hippo and TGF pathways in ICCs. Methods: The protein levels of yes-associated protein 1 (YAP1), MOB1, Smad2, and TGFβ2 in 88 ICC cases were analyzed. Protein level was graded by a scoring system; then, the clinicopathological factors, including prognosis, were analyzed based on protein level. Results: Nuclear overexpression of YAP1 was seen in 28 cases (31.8{\%}), and it was significantly associated with a poor overall survival rate (p = 0.01). MOB1 expression decreased in 42 cases (47.7{\%}) and was associated with a poor overall survival rate (p = 0.02). SMAD2 nuclear localization was significantly correlated with a high YAP1 level independent of TGFβ2. Multivariate analysis revealed that a high YAP1 level, a low MOB1 level, and lymphatic permeation were independent risk factors for overall survival. Conclusions: These results showed that key components of the Hippo signaling pathway are aberrantly expressed and associated with the malignant potential of human ICC.",
author = "Keishi Sugimachi and Miki Nishio and Shinichi Aishima and Yohsuke Kuroda and Tomohiro Iguchi and Hisateru Komatsu and Hidenari Hirata and Shotaro Sakimura and Hidetoshi Eguchi and Yuki Bekki and Kenji Takenaka and Yoshihiko Maehara and Akira Suzuki and Koshi Mimori",
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T1 - Altered Expression of Hippo Signaling Pathway Molecules in Intrahepatic Cholangiocarcinoma

AU - Sugimachi, Keishi

AU - Nishio, Miki

AU - Aishima, Shinichi

AU - Kuroda, Yohsuke

AU - Iguchi, Tomohiro

AU - Komatsu, Hisateru

AU - Hirata, Hidenari

AU - Sakimura, Shotaro

AU - Eguchi, Hidetoshi

AU - Bekki, Yuki

AU - Takenaka, Kenji

AU - Maehara, Yoshihiko

AU - Suzuki, Akira

AU - Mimori, Koshi

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N2 - Objective: MOB1, a core component of the Hippo signaling pathway, suppresses cell proliferation, and MOB1 liver conditional knockout mice develop intrahepatic cholangiocarcinoma (ICC). However, its clinical significance in human ICC has not been established. The aim of this study was to characterize protein levels and the role of Hippo and TGF pathways in ICCs. Methods: The protein levels of yes-associated protein 1 (YAP1), MOB1, Smad2, and TGFβ2 in 88 ICC cases were analyzed. Protein level was graded by a scoring system; then, the clinicopathological factors, including prognosis, were analyzed based on protein level. Results: Nuclear overexpression of YAP1 was seen in 28 cases (31.8%), and it was significantly associated with a poor overall survival rate (p = 0.01). MOB1 expression decreased in 42 cases (47.7%) and was associated with a poor overall survival rate (p = 0.02). SMAD2 nuclear localization was significantly correlated with a high YAP1 level independent of TGFβ2. Multivariate analysis revealed that a high YAP1 level, a low MOB1 level, and lymphatic permeation were independent risk factors for overall survival. Conclusions: These results showed that key components of the Hippo signaling pathway are aberrantly expressed and associated with the malignant potential of human ICC.

AB - Objective: MOB1, a core component of the Hippo signaling pathway, suppresses cell proliferation, and MOB1 liver conditional knockout mice develop intrahepatic cholangiocarcinoma (ICC). However, its clinical significance in human ICC has not been established. The aim of this study was to characterize protein levels and the role of Hippo and TGF pathways in ICCs. Methods: The protein levels of yes-associated protein 1 (YAP1), MOB1, Smad2, and TGFβ2 in 88 ICC cases were analyzed. Protein level was graded by a scoring system; then, the clinicopathological factors, including prognosis, were analyzed based on protein level. Results: Nuclear overexpression of YAP1 was seen in 28 cases (31.8%), and it was significantly associated with a poor overall survival rate (p = 0.01). MOB1 expression decreased in 42 cases (47.7%) and was associated with a poor overall survival rate (p = 0.02). SMAD2 nuclear localization was significantly correlated with a high YAP1 level independent of TGFβ2. Multivariate analysis revealed that a high YAP1 level, a low MOB1 level, and lymphatic permeation were independent risk factors for overall survival. Conclusions: These results showed that key components of the Hippo signaling pathway are aberrantly expressed and associated with the malignant potential of human ICC.

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