Concurrent analysis of human equilibrative nucleoside transporter 1 and ribonucleotide reductase subunit 1 expression increases predictive value for prognosis in cholangiocarcinoma patients treated with adjuvant gemcitabine-based chemotherapy

BACKGROUND: The aim of this study was to investigate the predictive and prognostic values of intratumoural human equilibrative nucleoside transporter 1 (hENT1) and ribonucleotide reductase subunit 1 (RRM1) expression in advanced cholangiocarcinoma patients treated with adjuvant gemcitabine-based chemotherapy (AGC). METHODS: Intratumoural hENT1 and RRM1 expression levels were investigated immunohistochemically in 127 patients with advanced cholangiocarcinoma who underwent surgical resection (68 with AGC and 59 without AGC). The impacts of hENT1 and RRM1 expression on survival were evaluated. RESULTS: High intratumoural hENT1 and RRM1 expression levels were observed in 86 (68%) and 67 (53%) patients, respectively. In a multivariate analysis of 68 patients who received AGC, high hENT1 (P=0.044) and low RRM1 expression (P=0.009) were independently associated with prolonged disease-free survival (DFS), whereas low RRM1 expression (P=0.024) was independently associated with prolonged overall survival (OS). Moreover, concurrent high hENT1 and low RRM1 expression was a powerful independent predictor of prolonged DFS (P<0.001) and OS (P=0.001) when the combined classification of hENT1 and RRM1 was introduced. CONCLUSIONS: Concurrent analysis of hENT1 and RRM1 expression may increase the predictive value of these biomarkers for survival of advanced cholangiocarcinoma patients treated with AGC.