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.
| Original language | English |
|---|---|
| Pages (from-to) | 67-74 |
| Number of pages | 8 |
| Journal | Oncology (Switzerland) |
| Volume | 93 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Jul 1 2017 |
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All Science Journal Classification (ASJC) codes
- Oncology
- Cancer Research
Cite this
Altered Expression of Hippo Signaling Pathway Molecules in Intrahepatic Cholangiocarcinoma. / Sugimachi, Keishi; Nishio, Miki; Aishima, Shinichi; Kuroda, Yosuke; Iguchi, Tomohiro; Komatsu, Hisateru; Hirata, Hidenari; Sakimura, Shotaro; Eguchi, Hidetoshi; Bekki, Yuki; Takenaka, Kenji; Maehara, Yoshihiko; Suzuki, Akira; Mimori, Koshi.
In: Oncology (Switzerland), Vol. 93, No. 1, 01.07.2017, p. 67-74.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Altered Expression of Hippo Signaling Pathway Molecules in Intrahepatic Cholangiocarcinoma
AU - Sugimachi, Keishi
AU - Nishio, Miki
AU - Aishima, Shinichi
AU - Kuroda, Yosuke
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
PY - 2017/7/1
Y1 - 2017/7/1
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.
UR - http://www.scopus.com/inward/record.url?scp=85018785069&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85018785069&partnerID=8YFLogxK
U2 - 10.1159/000463390
DO - 10.1159/000463390
M3 - Article
C2 - 28448997
AN - SCOPUS:85018785069
VL - 93
SP - 67
EP - 74
JO - Oncology
JF - Oncology
SN - 0030-2414
IS - 1
ER -