CXCL12 expression in intrahepatic cholangiocarcinoma is associated with metastasis and poor prognosis

Tatsunori Miyata, Yo Ichi Yamashita, Tomoharu Yoshizumi, Masayuki Shiraishi, Masayuki Ohta, Susumu Eguchi, Shinichi Aishima, Hikaru Fujioka, Hideo Baba

Research output: Contribution to journalArticle

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.

Original languageEnglish
JournalCancer Science
DOIs
Publication statusAccepted/In press - Jan 1 2019

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Cholangiocarcinoma
Neoplasm Metastasis
Liver
Oligonucleotide Array Sequence Analysis
Genes
Immunohistochemistry
Cell Line
Hepatectomy
Microarray Analysis
Paraffin
Formaldehyde
Gene Expression
Recurrence
Survival

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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CXCL12 expression in intrahepatic cholangiocarcinoma is associated with metastasis and poor prognosis. / Miyata, Tatsunori; Yamashita, Yo Ichi; Yoshizumi, Tomoharu; Shiraishi, Masayuki; Ohta, Masayuki; Eguchi, Susumu; Aishima, Shinichi; Fujioka, Hikaru; Baba, Hideo.

In: Cancer Science, 01.01.2019.

Research output: Contribution to journalArticle

Miyata, Tatsunori ; Yamashita, Yo Ichi ; Yoshizumi, Tomoharu ; Shiraishi, Masayuki ; Ohta, Masayuki ; Eguchi, Susumu ; Aishima, Shinichi ; Fujioka, Hikaru ; Baba, Hideo. / CXCL12 expression in intrahepatic cholangiocarcinoma is associated with metastasis and poor prognosis. In: Cancer Science. 2019.
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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.",
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AU - Ohta, Masayuki

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AU - Aishima, Shinichi

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