Gemcitabine sensitivity factors, hENT1 and RRM1 as potential prognostic biomarker for advanced biliary tract cancer

Ting Deng, Hong Pan, Ru Bing Han, Ding Zhi Huang, Hong Li Li, Li Kun Zhou, Xia Wang, Ming Bai, Xiang Li, Rui Liu, Shao Hua Ge, Tao Ning, L. Zhang, Y. Ba

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    9 Scopus citations

    Abstract

    Background and aims: Biliary tract caner (BTC) is one of rare malignant disease with poor prognosis. Gemcitabine has been widely used as chemotherapeutic agent for advanced BTC treatment. Several molecules involved in gemcitabine metabolism, including human equilibrative nucleoside transporter (hENT1) and ribonucleotide reductase subunit M1 (RRM1), have been investigated as predictive biomarkers of chemotherapy efficacy. The aim of present study is to determine whether hENT1 and RRM1 could be used as the biomarkers to assess the efficacy of chemotherapy and predict survival in patients with advanced BTC. Methods: The analysis was performed on samples from 44 patients with unresectable or recurrent BTC who were treated with gemcitabine as first-line therapy. We determined levels of hENT1 and RRM1 with immunohistochemistry (IHC). Also, its prognostic and predictive role on tumor response and several clinical factors for survival were evaluated with Kaplan-Meier or Cox analysis. Results: The patients who were clinical benefit (partial response [PR] or stable disease [SD]) had high level of hENT1 (P = 0.046) and low level of RRM1 (P = 0.033). Moreover, hENT1 expression was a significant factor for progression free survival (PFS) (P = 0.005) and overall survival (OS) (P = 0.048) in Cox univariate analysis. Also, hENT1 was an independent prognostic factor of OS based on Cox multivariate analysis (P = 0.005). Conclusions: The expression of hENT1 and RRM1 was associated with gemcitabine efficacy. hENT1 was one of reliable predictive marker of survival in patients with advanced BTC patients.

    Original languageEnglish (US)
    Pages (from-to)5041-5049
    Number of pages9
    JournalInternational Journal of Clinical and Experimental Medicine
    Volume7
    Issue number12
    StatePublished - Dec 30 2014

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    Keywords

    • Biliary tract cancer
    • Gemcitabine
    • Human equilibrative nucleoside transporter 1
    • Ribonucleotide reductase subunit M1

    ASJC Scopus subject areas

    • Biochemistry, Genetics and Molecular Biology(all)

    Cite this

    Deng, T., Pan, H., Han, R. B., Huang, D. Z., Li, H. L., Zhou, L. K., Wang, X., Bai, M., Li, X., Liu, R., Ge, S. H., Ning, T., Zhang, L., & Ba, Y. (2014). Gemcitabine sensitivity factors, hENT1 and RRM1 as potential prognostic biomarker for advanced biliary tract cancer. International Journal of Clinical and Experimental Medicine, 7(12), 5041-5049.