Abstract
The combination of gemcitabine plus cisplatin (GP) is regarded as a first-line treatment for patients with unresectable or recurrent biliary tract cancer (BTC). Several proteins including human equilibrative nucleoside transporter-1 (hENT1), deoxycytidine kinase (DCK), cytidine deaminase (CDA), and ribonucleotide reductase subunit 1 (RRM1) are known to be involved in gemcitabine uptake and metabolism. This study was aimed to identify the predictive and prognostic values of these biomarkers in patients who treated with GP for advanced BTC. Tumor samples were obtained from 34 patients with unresectable or recurrent BTC who were treated with GP between August 2015 and February 2018. Intratumoral expression of hENT1, DCK, CDA and RRM1 was determined by immunohistochemistry and analyzed for association with chemotherapy response, progression-free survival (PFS) and overall survival (OS). Median OS was significantly longer in the RRM1-negative group than in the RRM1-positive (9.9 months vs. 5.9 months, p = 0.037). Multivariate adjustment analyses also demonstrated RRM1 expression as an independent prognostic factor for OS in patients treated with GP chemotherapy. Increased intratumoral expression of RRM1 on immunohistochemical staining may be a biomarker predicting poor survival in patients with GP chemotherapy for advanced BTC. Large-scale well-predefined prospective research is needed to validate the utility of biomarkers in clinical practice.
Highlights
Biliary tract cancers (BTCs) are uncommon malignant neoplasms of the gastrointestinal tract, which consist of a group of heterogeneous tumors including gallbladder (GB) cancer, cholangiocarcinoma (CCA) of the extra- and intra-hepatic bile ducts, and the ampulla of Vater [1,2]
Several studies have reported that gemcitabine and gemcitabine-based chemotherapy regimens are effective in patients with advanced BTC, the combination of gemcitabine and cisplatin (GP) is accepted as the standard first-line chemotherapy in these patients [4,5,6,7]
In this study, we aimed to evaluate the predictive and prognostic value of key molecules in gemcitabine metabolism by analyzing the intratumoral expression in tumor samples and clarify which biomarker is the most reliable for patients treated with GP chemotherapy for unresectable, metastatic and recurrent BTC
Summary
Biliary tract cancers (BTCs) are uncommon malignant neoplasms of the gastrointestinal tract, which consist of a group of heterogeneous tumors including gallbladder (GB) cancer, cholangiocarcinoma (CCA) of the extra- and intra-hepatic bile ducts, and the ampulla of Vater [1,2]. Several transporters, including human equilibrative nucleoside transporter-1 (hENT1) and human concentrative nucleoside transporters (hCNT), and several enzymes, such as deoxycytidine kinase (DCK), deoxycytidine deaminase (CDA), and ribonucleotide reductase M1 (RRM1), were found to be involved in gemcitabine uptake and metabolism [8,9]. These proteins have been suggested as predictors for the efficacy of gemcitabine treatment and prognostic biomarkers in several cancer cell lines and specimens [10,11,12,13]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
