Prognostic predictive values of gemcitabine sensitivity-related gene products for unresectable or recurrent biliary trac
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RESEARCH
WORLD JOURNAL OF SURGICAL ONCOLOGY
Open Access
Prognostic predictive values of gemcitabine sensitivity-related gene products for unresectable or recurrent biliary tract cancer treated with gemcitabine alone Akihiro Murata, Ryosuke Amano*, Nobuya Yamada, Kenjiro Kimura, Masakazu Yashiro, Bunzo Nakata and Kosei Hirakawa
Abstract Background: Gemcitabine is a pyrimidine nucleoside analog that is a commonly used chemotherapeutic agent for unresectable or recurrent biliary tract cancer (BTC). Several molecules involved in gemcitabine metabolism, including human equilibrative nucleoside transporter (hENT1), deoxycytidine kinase (dCK), and ribonucleotide reductase subunit M1 (RRM1), have been investigated as predictive biomarkers of gemcitabine efficacy, mostly in pancreatic cancer. The aim of this study is to clarify which biomarker is the most reliable among hENT1, dCK, and RRM1 to predict survival in patients with advanced BTC treated with gemcitabine alone. Methods: The analysis was performed on samples from 28 patients with unresectable or recurrent BTC who were treated with gemcitabine alone as first-line therapy. The starting date of overall survival (OS) and progression-free survival (PFS) was defined as the date of first treatment with gemcitabine. Intratumoral hENT1, dCK, and RRM1 expressions were examined by immunohistochemistry. Results: The expressions of hENT1, dCK, and RRM1 had no significant relationships with age, gender, primary tumor site, recurrence/unresectable, or histological type. Among the three molecules, only hENT1 expression was a significant factor affecting OS and PFS in univariate analysis; OS was 11.4 months for high hENT1 expression versus 5.7 months for low, P = 0.0057; PFS was 7.7 months for high versus 2.5 months for low, P = 0.0065. Multivariate analyses also identified hENT1 expression as an independent predictive factor for OS. Conclusions: hENT1 is the most reliable predictive marker of survival in patients with advanced BTC treated with gemcitabine. Keywords: Biliary tract cancer, Deoxycytidine kinase, Gemcitabine, Human equilibrative nucleoside transporter 1, Ribonucleotide reductase subunit M1
Background Biliary tract cancer (BTC) is relatively rare, but its incidence is increasing worldwide. The prevalence is much higher in East Asia and Latin America than in Europe and the United States [1,2]. Although a complete surgical resection is the only curative modality, most patients are not eligible for surgery because of the advanced stage of disease at diagnosis. Moreover, even patients who undergo * Correspondence: [email protected] Department of Surgical Oncology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan
a surgical resection often have a recurrence of the disease. The outcome for patients with unresectable or recurrent BTC is dismal and their median survival is usually under 1 year [3]. Most patients with unresectable or recurrent BTC are therefore candidates for palliative chemotherapy. Gemcitabine
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