RRC ID 60129
Author Miyata T, Yamashita YI, Yoshizumi T, Shiraishi M, Ohta M, Eguchi S, Aishima S, Fujioka H, Baba H.
Title CXCL12 expression in intrahepatic cholangiocarcinoma is associated with metastasis and poor prognosis.
Journal Cancer Sci
Abstract Intrahepatic cholangiocarcinoma is a rare malignant biliary neoplasm that causes a poor prognosis even after curative hepatectomy. Liver metastasis is the major recurrence pattern of intrahepatic cholangiocarcinoma; therefore, the prevention of liver metastasis is a desirable objective. The aim of this study is to identify gene(s) related to liver metastasis of intrahepatic cholangiocarcinoma and to examine the inhibitory effects on metastasis of intrahepatic cholangiocarcinoma by controlling such gene(s). We collected 3 pairs of intrahepatic cholangiocarcinoma frozen samples, and 36 pairs (primary and metastatic lesions) of intrahepatic cholangiocarcinoma formalin-fixed paraffin-embedded samples, from patients who underwent surgical resection at hospitals related to the Kyushu Study Group of Liver Surgery between 2002 and 2016. We carried out cDNA microarray analyses and immunohistochemistry to identify candidate genes, and evaluated one of them as a therapeutic target using human cholangiocarcinoma cell lines. We identified 4 genes related to liver metastasis using cDNA microarray, and found that CXCL12 was the only gene whose expression was significantly higher in liver metastasis than in primary intrahepatic cholangiocarcinoma by immunohistochemistry (P = .003). In prognosis, patients in the high CXCL12 group showed a significantly poor prognosis in disease-free (P < .0001) and overall survival (P = .0004). By knockdown of CXCL12, we could significantly suppress the invasive and migratory capabilities of 2 human cholangiocarcinoma cell lines. Therefore, CXCL12 might be associated with metastasis and poor prognosis in intrahepatic cholangiocarcinoma.
Volume 110(10)
Pages 3197-3203
Published 2019-10-1
DOI 10.1111/cas.14151
PMID 31361379
PMC PMC6778649
MeSH Aged Bile Duct Neoplasms / genetics Bile Duct Neoplasms / metabolism Bile Duct Neoplasms / pathology* Cell Line, Tumor Cell Movement Chemokine CXCL12 / genetics* Chemokine CXCL12 / metabolism* Cholangiocarcinoma / genetics Cholangiocarcinoma / metabolism Cholangiocarcinoma / pathology* Female Gene Expression Profiling Gene Expression Regulation, Neoplastic Humans Liver Neoplasms / genetics Liver Neoplasms / metabolism Liver Neoplasms / pathology Liver Neoplasms / secondary* Middle Aged Oligonucleotide Array Sequence Analysis / methods Prognosis Up-Regulation
IF 4.751
Times Cited 4
Human and Animal Cells SSP-25(RCB1293) HuH-28(RCB1943)