Establishment of six new human biliary tract carcinoma cell lines and identification of MAGEH1 as a candidate biomarker for predicting the efficacy of gemcitabine treatment

• Published in: Cancer science Vol. 101; no. 4; pp. 882 - 888
• Main Authors: Ojima, Hidenori, Yoshikawa, Daitaro, Ino, Yoshihiro, Shimizu, Hiroko, Miyamoto, Masashi, Kokubu, Akiko, Hiraoka, Nobuyoshi, Morofuji, Noriaki, Kondo, Tadashi, Onaya, Hiroaki, Okusaka, Takuji, Shimada, Kazuaki, Sakamoto, Yoshihiro, Esaki, Minoru, Nara, Satoshi, Kosuge, Tomoo, Hirohashi, Setsuo, Kanai, Yae, Shibata, Tatsuhiro
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.04.2010; Blackwell; John Wiley & Sons, Inc
• Subjects: Animals; Antimetabolites, Antineoplastic - therapeutic use; Bile Duct Neoplasms - drug therapy; Bile Duct Neoplasms - metabolism; Bile ducts; Biliary tract; Biliary Tract Neoplasms - drug therapy; Biliary Tract Neoplasms - metabolism; Biological and medical sciences; Biomarkers; Cancer therapies; Carcinoma; Cell culture; Chemotherapy; Cytotoxicity; Deoxycytidine - analogs & derivatives; Deoxycytidine - therapeutic use; Female; Gemcitabine; Gene expression; Gene Expression Profiling; Genes; Genomes; Humans; Immunodeficiency; Medical prognosis; Medical sciences; Mice; Mice, SCID; Microtubule-Associated Proteins; Neoplasm Proteins; Original; Pathogens; Physiology; Specific Pathogen-Free Organisms; Tumor cell lines; Tumor cells; Tumors; Xenografts; United States > US; Japan; Antineoplastic agent; Human; Biliary tract; Carcinoma; Gemcitabine; Digestive system; Treatment efficiency; Biological marker; Malignant tumor; Cancerology; Treatment; Antimetabolic; Established cell line; Pyrimidine derivatives; Fluorine Organic compounds; Pyrimidine nucleoside; Cancer
• ISSN: 1347-9032; 1349-7006; 1349-7006
• DOI: 10.1111/j.1349-7006.2009.01462.x

The aim of this study was to establish new biliary tract carcinoma (BTC) cell lines and identify predictive biomarkers for the potential effectiveness of gemcitabine therapy. Surgical specimens of BTC were transplanted directly into immunodeficient mice to establish xenografts, then subjected to in vitro cell culture. The gemcitabine sensitivity of each cell line was determined and compared with the genome‐wide gene expression profile. A new predictive biomarker candidate was validated using an additional cohort of gemcitabine‐treated BTC cases. From 55 BTC cases, we established 19 xenografts and six new cell lines. Based on their gemcitabine sensitivity, 10 BTC cell lines (including six new and four publicly available ones) were clearly categorized into two groups, and MAGEH1 mRNA expression in the tumor cells showed a significant negative correlation with their sensitivity to gemcitabine. Immunohistochemically, MAGEH1 protein was detected in three (50%) out of six sensitive cell lines, and four (100%) out of four resistant cell lines. In the validation cohort of gemcitabine‐treated recurrence cases, patients were categorized into “effective” and “non‐effective” groups according to the RECIST guidelines for assessment of chemotherapeutic effects. MAGEH1 protein expression was detected in two (40%) out of five “effective” cases and all four (100%) “non‐effective” cases. We have established a new BTC bioresource that covers a wide range of biological features, including drug sensitivity, and is linked with clinical information. Negative expression of MAGEH1 protein serves as a potential predictive marker for the effectiveness of gemcitabine therapy in BTC. (Cancer Sci 2010; 101: 882–888)