title: Gemcitabine sensitivity factors, hENT1 and RRM1 as potential prognostic biomarker for advanced biliary tract cancer.
abstract: OBJECTIVE
  Biliary tract caner (BTC) is one of rare malignant disease with poor prognosis. Gemcitabine has been widely used as chemotherapeutic agent for advanced BTC treatment. Several molecules involved in gemcitabine metabolism, including human equilibrative nucleoside transporter (hENT1) and ribonucleotide reductase subunit M1 (RRM1), have been investigated as predictive biomarkers of chemotherapy efficacy. The aim of present study is to determine whether hENT1 and RRM1 could be used as the biomarkers to assess the efficacy of chemotherapy and predict survival in patients with advanced BTC.
  
  
  METHODS
  The analysis was performed on samples from 44 patients with unresectable or recurrent BTC who were treated with gemcitabine as first-line therapy. We determined levels of hENT1 and RRM1 with immunohistochemistry (IHC). Also, its prognostic and predictive role on tumor response and several clinical factors for survival were evaluated with Kaplan-Meier or Cox analysis.
  
  
  RESULTS
  The patients who were clinical benefit (partial response [PR] or stable disease [SD]) had high level of hENT1 (P = 0.046) and low level of RRM1 (P = 0.033). Moreover, hENT1 expression was a significant factor for progression free survival (PFS) (P = 0.005) and overall survival (OS) (P = 0.048) in Cox univariate analysis. Also, hENT1 was an independent prognostic factor of OS based on Cox multivariate analysis (P = 0.005).
  
  
  CONCLUSIONS
  The expression of hENT1 and RRM1 was associated with gemcitabine efficacy. hENT1 was one of reliable predictive marker of survival in patients with advanced BTC patients.
authors: Department of Gastrointestinal Medical Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy Tianjin 300060, China.
authors: Ting
authors: T
authors: Deng
authors: Department of Gastrointestinal Medical Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy Tianjin 300060, China.
authors: Hong
authors: H
authors: Pan
authors: Department of Gastrointestinal Medical Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy Tianjin 300060, China.
authors: Rubing
authors: R
authors: Han
authors: Department of Gastrointestinal Medical Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy Tianjin 300060, China.
authors: Dingzhi
authors: D
authors: Huang
authors: Department of Gastrointestinal Medical Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy Tianjin 300060, China.
authors: Hongli
authors: H
authors: Li
authors: Department of Gastrointestinal Medical Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy Tianjin 300060, China.
authors: Likun
authors: L
authors: Zhou
authors: Department of Gastrointestinal Medical Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy Tianjin 300060, China.
authors: Xia
authors: X
authors: Wang
authors: Department of Gastrointestinal Medical Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy Tianjin 300060, China.
authors: Ming
authors: M
authors: Bai
authors: Department of Gastrointestinal Medical Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy Tianjin 300060, China.
authors: Xiang
authors: X
authors: Li
authors: Department of Gastrointestinal Medical Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy Tianjin 300060, China.
authors: Rui
authors: R
authors: Liu
authors: Department of Gastrointestinal Medical Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy Tianjin 300060, China.
authors: Shaohua
authors: S
authors: Ge
authors: Department of Gastrointestinal Medical Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy Tianjin 300060, China.
authors: Tao
authors: T
authors: Ning
authors: Department of Gastrointestinal Medical Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy Tianjin 300060, China.
authors: Le
authors: L
authors: Zhang
authors: Department of Gastrointestinal Medical Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy Tianjin 300060, China.
authors: Yi
authors: Y
authors: Ba
keywords: Biliary tract cancer; gemcitabine; human equilibrative nucleoside transporter 1; ribonucleotide reductase subunit M1