title: 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.
abstract: 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.
authors.affiliation: Pathology Division, Clinical Trials and Practice Support Division, Center for Cancer Control and Information Services, National Cancer Center, Chuo-ku, Tokyo, Japan.
authors.forename: Hidenori
authors.initials: H
authors.lastname: Ojima
authors.forename: Daitaro
authors.initials: D
authors.lastname: Yoshikawa
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Ino
authors.forename: Hiroko
authors.initials: H
authors.lastname: Shimizu
authors.forename: Masashi
authors.initials: M
authors.lastname: Miyamoto
authors.forename: Akiko
authors.initials: A
authors.lastname: Kokubu
authors.forename: Nobuyoshi
authors.initials: N
authors.lastname: Hiraoka
authors.forename: Noriaki
authors.initials: N
authors.lastname: Morofuji
authors.forename: Tadashi
authors.initials: T
authors.lastname: Kondo
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Onaya
authors.forename: Takuji
authors.initials: T
authors.lastname: Okusaka
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Shimada
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Sakamoto
authors.forename: Minoru
authors.initials: M
authors.lastname: Esaki
authors.forename: Satoshi
authors.initials: S
authors.lastname: Nara
authors.forename: Tomoo
authors.initials: T
authors.lastname: Kosuge
authors.forename: Setsuo
authors.initials: S
authors.lastname: Hirohashi
authors.forename: Yae
authors.initials: Y
authors.lastname: Kanai
authors.forename: Tatsuhiro
authors.initials: T
authors.lastname: Shibata
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D001650:Bile Duct Neoplasms / Q000188:drug therapy / Q000378:metabolism; D001661:Biliary Tract Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D013047:Specific Pathogen-Free Organisms; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D003841:Deoxycytidine; C076744:cytoplasmic linker protein 170; D000093542:Gemcitabine