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Prognostic Impact of Human Equilibrative Nucleoside Transporter 1 and Ribonucleotid Reductase Submit 1 Expression in Cholangiocarcinoma Patients Treated With Adjuvant Gemcitabine-Based Chemotherapy
Hayato Sasaki^*, Yoshiaki Murakami, Kenichiro Uemura, Takeshi Sudo, Yasushi Hashimoto, Naru Kondo, Taijiro Sueda
Gastrointestinal Surgery, Hiroshima University Hospital, Hiroshima, Japan

Background: The efficacy of AGC varies among individuals and the resulting survival rates are still unsatisfactory. Objective: The aim of this study was to investigate predictive value of intratumoral human equilibrative nucleoside transporter 1 (hENT1) and ribonucleotid reductase submit 1 (RRM1) expression for advanced cholangiocarcinoma patients treated with adjuvant gemcitabine-based chemotherapy (AGC) after surgical resection. Methods: Intratumoral hENT1 and RRM1 expression was investigated immunohistochemically in 127 patients with advanced cholangiocarcinoma who underwent surgical resection (including 68 with AGC, and 59 without AGC). Impact of hENT1 and RRM1 expression on disease-free survival (DFS) and overall survival (OS) were evaluated by univariate and multivariate analyses. Results: High intratumoral hENT1 and RRM1 expression was observed in 86 (68%) and 67 (53%) patients, respectively. Univariate analysis of data from 68 patients with AGC revealed that high hENT1 and low RRM1 expression were significantly associated with longer DFS (hENT1, P = 0.005; RRM1, P = 0.015) and longer OS (hENT1, P = 0.036; RRM1, P = 0.035). In multivariate analysis, moderately or poorly differentiation, (P = 0.007), low hENT1expression (P = 0.044) and high RRM1 expression (P = 0.009) were identified as independent risk factors for poor DFS, and moderately or poorly differentiation, (P = 0.045), lymph node metastasis, (P = 0.011) and high RRM1 expression (P = 0.009) were identified as independent risk factors for poor OS. In contrast, hENT1 and RRM1 expression did not correlate with DFS and OS in 58 patients without AGC. Conclusions: Intratumoral hENT1 and RRM1 expression predicts survival of advanced cholangiocarcinoma patients treated with AGC.

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