Role of Human Equilibrative Nucleoside Transporter 1 (hENT1) in Intrahepatic Cholangiocarcinoma

There are few data reporting significant biological prognostic markers for iCCA affected patients. There is substantial interest in identifying and validating molecular markers to select patients with a high likelihood of benefiting from specific chemotherapy regimens. The aim of this study was to evaluate whether the intratumoral expression of hENT1, besides being a predictor of response to adjuvant Gemcitabine chemotherapy in iCCA, as we have previously demonstrated, may also represent a prognostic factor in iCCAs and may be related to the expression of tumor aggressiveness markers, Ki67 and p53. This study has permitted to evaluate the role of membrane hENT1 in iCCA cells growth. The immunohistochemistry analysis on 40 patients affected of iCCA revealed that in tumor tissues hENT1 protein could be differently expressed (negative, moderate or high) but surely, it has to be expressed on cell membrane in order to carry out its role of nucleoside transporter. Our results demonstrate a significant positive correlation between membrane hENT1 expression and ki67 score; in these terms, hENT1 would represent the intrinsic cellular key to tumor growth, being consequently related to worse prognosis. hENT1 mRNA expression and protein levels continued to be poorly understood. Various factors that influence hENT1 expression have been identified; in this study we hypothesized that hENT1 expression may be influenced from cell cycle related factors and consequently we investigated the relationship between hENT1 and mutated p53 expression in iCCA. Our finding on 40 iCCA affected patients and on cell lines suggest a significant correlation between the expression of mutated p53 and hENT1. In conclusion, membrane hENT1 seemed to characterize tumors with a high growth rate and the expression of hENT1 in iCCAs correlate with mutated p53. hENT1, besides being a predictive factor of response to adjuvant Gemcitabine, represent also a negative prognostic factor in iCCAs affected patients.