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.
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.
Ojima
Hidenori
H
Pathology Division, Clinical Trials and Practice Support Division, Center for Cancer Control and Information Services, National Cancer Center, Chuo-ku, Tokyo, Japan.
Yoshikawa
Daitaro
D
Ino
Yoshihiro
Y
Shimizu
Hiroko
H
Miyamoto
Masashi
M
Kokubu
Akiko
A
Hiraoka
Nobuyoshi
N
Morofuji
Noriaki
N
Kondo
Tadashi
T
Onaya
Hiroaki
H
Okusaka
Takuji
T
Shimada
Kazuaki
K
Sakamoto
Yoshihiro
Y
Esaki
Minoru
M
Nara
Satoshi
S
Kosuge
Tomoo
T
Hirohashi
Setsuo
S
Kanai
Yae
Y
Shibata
Tatsuhiro
T
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
D000964:Antimetabolites, Antineoplastic; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D003841:Deoxycytidine; C076744:cytoplasmic linker protein 170; D000093542:Gemcitabine