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

Hidenori Ojima, Daitaro Yoshikawa, Yoshihiro Ino, Hiroko Shimizu, Masashi Miyamoto, Akiko Kokubu, Nobuyoshi Hiraoka, Noriaki Morofuji, Tadashi Kondo, Hiroaki Onaya, Takuji Okusaka, Kazuaki Shimada, Yoshihiro Sakamoto, Minoru Esaki, Satoshi Nara, Tomoo Kosuge, Setsuo Hirohashi, Yae Kanai, Tatsuhiro Shibata

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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.

Original languageEnglish
Pages (from-to)882-888
Number of pages7
JournalCancer Science
Volume101
Issue number4
DOIs
Publication statusPublished - 2010 Apr
Externally publishedYes

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gemcitabine
Biliary Tract
Biomarkers
Carcinoma
Cell Line
Heterografts
Proteins
Transcriptome
Cell Culture Techniques

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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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. / 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.

In: Cancer Science, Vol. 101, No. 4, 04.2010, p. 882-888.

Research output: Contribution to journalArticle

Ojima, H, Yoshikawa, D, Ino, Y, Shimizu, H, Miyamoto, M, Kokubu, A, Hiraoka, N, Morofuji, N, Kondo, T, Onaya, H, Okusaka, T, Shimada, K, Sakamoto, Y, Esaki, M, Nara, S, Kosuge, T, Hirohashi, S, Kanai, Y & Shibata, T 2010, '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', Cancer Science, vol. 101, no. 4, pp. 882-888. https://doi.org/10.1111/j.1349-7006.2009.01462.x
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. / 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. In: Cancer Science. 2010 ; Vol. 101, No. 4. pp. 882-888.
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AU - Ino, Yoshihiro

AU - Shimizu, Hiroko

AU - Miyamoto, Masashi

AU - Kokubu, Akiko

AU - Hiraoka, Nobuyoshi

AU - Morofuji, Noriaki

AU - Kondo, Tadashi

AU - Onaya, Hiroaki

AU - Okusaka, Takuji

AU - Shimada, Kazuaki

AU - Sakamoto, Yoshihiro

AU - Esaki, Minoru

AU - Nara, Satoshi

AU - Kosuge, Tomoo

AU - Hirohashi, Setsuo

AU - Kanai, Yae

AU - Shibata, Tatsuhiro

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N2 - 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.

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