TY - JOUR
T1 - Gamma-synuclein is a novel prognostic marker that promotes tumor cell migration in biliary tract carcinoma
AU - Takemura, Yusuke
AU - Ojima, Hidenori
AU - Oshima, Go
AU - Shinoda, Masahiro
AU - Hasegawa, Yasushi
AU - Kitago, Minoru
AU - Yagi, Hiroshi
AU - Abe, Yuta
AU - Hori, Shutaro
AU - Fujii-Nishimura, Yoko
AU - Kubota, Naoto
AU - Masuda, Yuki
AU - Hibi, Taizo
AU - Sakamoto, Michiie
AU - Kitagawa, Yuko
N1 - Funding Information:
We are grateful to members of the Department of Pathology, Division of Cellular Signaling, Institute for Advanced Medical Research, and the Collaborative Research Resources at Keio University School of Medicine for technical assistance. We thank Dr. Ryo Takemura, who is a member of the Biostatistics Unit, Clinical and Translational Research Center at Keio University, for advice on the statistical analyses. We also would like to thank Mr. David Smallbones for detailed English editing. This work was supported by JSPS KAKENHI. Hibi T received JSPS KAKENHI Grant No. 16K10609. Ojima H and Sakamoto M also received JSPS KAKENHI Grant No. 17K08769.
Funding Information:
We are grateful to members of the Department of Pathology, Division of Cellular Signaling, Institute for Advanced Medical Research, and the Collaborative Research Resources at Keio University School of Medicine for technical assistance. We thank Dr. Ryo Takemura, who is a member of the Biostatistics Unit, Clinical and Translational Research Center at Keio University, for advice on the statistical analyses. We also would like to thank Mr. David Smallbones for detailed English editing. This work was supported by JSPS KAKENHI. Hibi T received JSPS KAKENHI Grant No. 16K10609. Ojima H and Sakamoto M also received JSPS KAKENHI Grant No. 17K08769.
Publisher Copyright:
© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
PY - 2021/8
Y1 - 2021/8
N2 - Gamma-synuclein (SNCG) promotes invasive behavior and is reportedly a prognostic factor in a range of cancers. However, its role in biliary tract carcinoma (BTC) remains unknown. Consequently, we investigated the clinicopathological significance and function of SNCG in BTC. Using resected BTC specimens from 147 patients with adenocarcinoma (extrahepatic cholangiocarcinoma [ECC, n = 96]; intrahepatic cholangiocarcinoma [ICC, n = 51]), we immunohistochemically evaluated SNCG expression and investigated its correlation with clinicopathological factors and outcomes. Furthermore, cell lines with high SNCG expression were selected from 16 BTC cell lines and these underwent cell proliferation and migration assays by siRNAs. In the results, SNCG expression was present in 22 of 96 (22.9%) ECC patients and in 10 of 51 (19.6%) ICC patients. SNCG expression was significantly correlated with poorly differentiated tumor in both ECC and ICC (p = 0.01 and 0.03, respectively) and with perineural invasion and lymph node metastases in ECC (p = 0.04 and 0.003, respectively). Multivariate analyses revealed that SNCG expression was an independent poor prognostic factor in both OS and RFS in both ECC and ICC. In vitro analyses showed high SNCG expression in three BTC cell lines (NCC-BD1, NCC-BD3, and NCC-CC6-1). Functional analysis revealed that SNCG silencing could suppress cell migration in NCC-BD1 and NCC-CC6-1 and downregulate cell proliferation in NCC-CC6-1 significantly. In conclusion, SNCG may promote tumor cell activity and is potentially a novel prognostic marker in BTC.
AB - Gamma-synuclein (SNCG) promotes invasive behavior and is reportedly a prognostic factor in a range of cancers. However, its role in biliary tract carcinoma (BTC) remains unknown. Consequently, we investigated the clinicopathological significance and function of SNCG in BTC. Using resected BTC specimens from 147 patients with adenocarcinoma (extrahepatic cholangiocarcinoma [ECC, n = 96]; intrahepatic cholangiocarcinoma [ICC, n = 51]), we immunohistochemically evaluated SNCG expression and investigated its correlation with clinicopathological factors and outcomes. Furthermore, cell lines with high SNCG expression were selected from 16 BTC cell lines and these underwent cell proliferation and migration assays by siRNAs. In the results, SNCG expression was present in 22 of 96 (22.9%) ECC patients and in 10 of 51 (19.6%) ICC patients. SNCG expression was significantly correlated with poorly differentiated tumor in both ECC and ICC (p = 0.01 and 0.03, respectively) and with perineural invasion and lymph node metastases in ECC (p = 0.04 and 0.003, respectively). Multivariate analyses revealed that SNCG expression was an independent poor prognostic factor in both OS and RFS in both ECC and ICC. In vitro analyses showed high SNCG expression in three BTC cell lines (NCC-BD1, NCC-BD3, and NCC-CC6-1). Functional analysis revealed that SNCG silencing could suppress cell migration in NCC-BD1 and NCC-CC6-1 and downregulate cell proliferation in NCC-CC6-1 significantly. In conclusion, SNCG may promote tumor cell activity and is potentially a novel prognostic marker in BTC.
KW - biliary tract carcinoma
KW - gamma-synuclein
KW - immunohistochemistry
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U2 - 10.1002/cam4.4121
DO - 10.1002/cam4.4121
M3 - Article
C2 - 34245137
AN - SCOPUS:85109392173
SN - 2045-7634
VL - 10
SP - 5599
EP - 5613
JO - Cancer Medicine
JF - Cancer Medicine
IS - 16
ER -
