RRC ID 66966
Author Takemura Y, Ojima H, Oshima G, Shinoda M, Hasegawa Y, Kitago M, Yagi H, Abe Y, Hori S, Fujii-Nishimura Y, Kubota N, Masuda Y, Hibi T, Sakamoto M, Kitagawa Y.
Title Gamma-synuclein is a novel prognostic marker that promotes tumor cell migration in biliary tract carcinoma.
Journal Cancer Med
Abstract 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.
Volume 10(16)
Pages 5599-5613
Published 2021-8-1
DOI 10.1002/cam4.4121
PMID 34245137
PMC PMC8366101
MeSH Aged Aged, 80 and over Bile Duct Neoplasms / mortality* Bile Duct Neoplasms / pathology Bile Duct Neoplasms / surgery Bile Ducts, Extrahepatic / pathology Bile Ducts, Extrahepatic / surgery Bile Ducts, Intrahepatic / pathology Bile Ducts, Intrahepatic / surgery Biomarkers, Tumor / analysis Biomarkers, Tumor / genetics Biomarkers, Tumor / metabolism* Cell Line, Tumor Cell Movement Cholangiocarcinoma / mortality* Cholangiocarcinoma / pathology Cholangiocarcinoma / surgery Disease-Free Survival Female Follow-Up Studies Gene Knockdown Techniques Humans Male Middle Aged Neoplasm Proteins / analysis Neoplasm Proteins / genetics Neoplasm Proteins / metabolism* Prognosis gamma-Synuclein / analysis gamma-Synuclein / genetics gamma-Synuclein / metabolism*
IF 3.491
Human and Animal Cells TKKK(RCB1907) HuCCT1(RCB1960)