Deng Ting, Pan Hong, Han Rubing, Huang Dingzhi, Li Hongli, Zhou Likun, Wang Xia, Bai Ming, Li Xiang, Liu Rui, Ge Shaohua, Ning Tao, Zhang Le, Ba Yi
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.
Int J Clin Exp Med. 2014 Dec 15;7(12):5041-9. eCollection 2014.
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.
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.
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).
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.
胆管癌（BTC）是一种预后较差的罕见恶性疾病。吉西他滨已被广泛用作晚期BTC治疗的化疗药物。几种参与吉西他滨代谢的分子，包括人平衡核苷转运体（hENT1）和核糖核苷酸还原酶亚基M1（RRM1），已被研究作为化疗疗效的预测生物标志物。本研究的目的是确定hENT1和RRM1是否可作为评估晚期BTC患者化疗疗效和预测生存的生物标志物。
对44例不可切除或复发性BTC患者的样本进行分析，这些患者接受吉西他滨作为一线治疗。我们通过免疫组织化学（IHC）测定hENT1和RRM1的水平。此外，通过Kaplan-Meier或Cox分析评估其对肿瘤反应的预后和预测作用以及几个生存的临床因素。
临床获益（部分缓解[PR]或疾病稳定[SD]）的患者hENT1水平较高（P = 0.046），RRM1水平较低（P = 0.033）。此外，在Cox单因素分析中，hENT1表达是无进展生存期（PFS）（P = 0.005）和总生存期（OS）（P = 0.048）的重要因素。同样，基于Cox多因素分析，hENT1是OS的独立预后因素（P = 0.005）。
hENT1和RRM1的表达与吉西他滨疗效相关。hENT1是晚期BTC患者生存的可靠预测标志物之一。
