Human equilibrative nucleoside transporter 1 (hENT1) and deoxycytidine kinase (DCK) are predictive biomarkers for Gemcitabine-based chemoradiotherapy in resected pancreatic cancer patients: a retrospective cohort study

Abstract

Background and Aim Pancreatic cancer is reported to be one of the cancer-related deaths all over the world. Gemcitabine has been identified as one of the important therapies of malignant diseases. Gemcitabine cellular uptake is allowed by the transporter protein, human equilibrative nucleoside transporter 1 (hENT1). Gemcitabine is phosphorylated by deoxycytidine kinase (dCK) to its active metabolites intracellularly. This study aimed to determine retrospectively the correlation between hENT1 and dCK expression by immunohistochemistry and the overall survival outcome in pancreatic cancer patients who underwent resection and received gemcitabine chemotherapy postoperatively. Materials and methods The immunohistochemical analysis was accomplished on samples from 140 patients, who underwent pancreatic cancer resection and was treated by gemcitabine. Immunostaining was done by two expert pathologists and both are blind to patient’s characteristics. The intensity of staining of the tumor determines the scoring for hENT1 and dCK. Results Of the 140 tissue samples, 73 (52.1%) had detectable hENT1 cell membrane immunostaining and 67 samples (47.8%) without detectable hENT1. Patients who showed no significant hENT1 immunostaining had a median survival of 6 months, while patients who showed significant hENT1 staining had a median survival longer by 17 months. Of the 140 tissue samples, 52 (37.1%) had detectable dCK cytoplasmic immunostaining and 88 samples (62.9%) without detectable dCK. Patients who showed no significant dCK immunostaining had a median survival of 6.57 months, while patients who showed significant dCK staining had a median survival longer by 19 months. Conclusion In patients who received gemcitabine after pancreatic resection, a high expression of hENT1 and dCK are significantly correlated with a longer survival. In addition, in patients who underwent pancreatic cancer resection, immunohistochemical analysis of hENT1 and dCK are considered significant predictive markers to choose patients responding to gemcitabine therapy.

Keywords

• deoxycytidine kinase; gemcitabine; human equilibrative nucleoside transporter 1