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. 2014 Sep 23;111(7):1275-84.
doi: 10.1038/bjc.2014.399. Epub 2014 Jul 17.

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

H Sasaki  1 , Y Murakami  1 , K Uemura  1 , T Sudo  1 , Y Hashimoto  1 , N Kondo  1 , T Sueda  1
Affiliations

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

H Sasaki et al. Br J Cancer. .

Abstract

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.

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Figures

Figure 1
Figure 1
Immunohistochemical analysis of human equilibrative nucleoside transporter 1 (hENT1) and ribonucleotide reductase subunit 1 (RRM1) expression in cholangiocarcinoma. These photomicrographs reveal (A) high hENT1 expression, (B) low hENT1 expression, (C) high RRM1 expression, (D) low RRM1 expression (original magnification, × 200; bar=50 μm). Positive internal controls is established by staining of lymphocytes and stromal cells (arrows).
Figure 2
Figure 2
Disease-free survival (DFS) and overall survival (OS) curves stratified by intratumoural hENT1 expression. AGC (+) indicates subgroups of patients who received adjuvant gemcitabine-based chemotherapy; AGC (−) indicates subgroups of patients who did not receive adjuvant gemcitabine-based chemotherapy. (A) DFS curves in AGC (+) patients (P=0.005). (B) DFS curves in AGC (−) patients (P=0.796). (C) OS curves in AGC (+) patients (P=0.036). (D) OS curves in AGC (−) patients (P=0.913).
Figure 3
Figure 3
DFS and OS curves stratified by intratumoural RRM1 expression. AGC (+) indicates subgroups of patients who received adjuvant gemcitabine-based chemotherapy; AGC (−) indicates subgroups of patients who did not receive adjuvant gemcitabine-based chemotherapy. (A) DFS curves in AGC (+) patients (P=0.015). (B) DFS curves in AGC (−) patients (P=0.642). (C) OS curves in AGC (+) patients (P=0.035). (D) OS curves in AGC (−) patients (P=0.883).
Figure 4
Figure 4
DFS and OS curves stratified by combined analysis of intratumoural hENT1 and RRM1 expression. AGC (+) indicates subgroups of patients who received adjuvant gemcitabine-based chemotherapy; AGC (−) indicates subgroups of patients who did not receive adjuvant gemcitabine-based chemotherapy. (A) DFS curves in AGC (+) patients (P=0.003). (B) DFS curves in AGC (−) patients (P=0.778). (C) OS curves in AGC (+) patients (P=0.015). (D) OS curves in AGC (−) patients (P=0.994).
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