Medical Oncology, University Campus Bio-Medico, Rome, Italy.
J Cell Physiol. 2010 May;223(2):384-8. doi: 10.1002/jcp.22045.
Nucleoside transporter proteins are specialized proteins that mediate the transport of nucleosides and nucleoside analog drugs across the plasma membrane. The human equilibrative nucleoside transporter 1 (hENT1) is a member of these proteins and mediates cellular entry of gemcitabine, cytarabine, and fludarabine. The hENT1 expression has been demonstrated to be related with prognosis and activity of gemcitabine-based therapy in breast, ampullary, lung, and pancreatic cancer. We investigated the immunohistochemical expression of hENT in tumor samples from 111 patients with resected gastric adenocarcinoma, correlating these data with clinical parameters and disease outcomes. None of the patients received chemotherapy or radiation therapy before or after surgery as a part of an adjuvant or neoadjuvant program. On univariate survival analysis, the hENT1 expression was associated with overall survival (OS) and disease free survival (DFS). Specifically, those patients with overexpression of hENT1 showed a shorter OS (P = 0.021) and a shorter DFS (P = 0.033). Considering only the node positive patients, higher hENT levels were associated with significantly shorter median DFS (21.7 months; 95% CI 11.1-32.4) compared with patients with low expression of hENT1. The hENT1 expression was defined, in the lymph-node positive patients, as an independent prognostic factor (P = 0.019). Furthermore, considering only patients with diffuse or mixed tumors and lymph-node positive, the expression of hENT1 was strongly related with DFS and OS. Immunohistochemistry for the hENT1 protein carries prognostic information in patients with resected gastric cancer and holds promise as a predictive factor in chemotherapy decisions.
核苷转运蛋白是一类专门的蛋白质，可介导核苷和核苷类似物药物穿过质膜的转运。人嘧啶核苷转运蛋白 1（hENT1）是这些蛋白质中的一员，可介导吉西他滨、阿糖胞苷和氟达拉滨进入细胞。hENT1 的表达已被证明与乳腺癌、壶腹癌、肺癌和胰腺癌中吉西他滨为基础的治疗的预后和疗效相关。我们研究了 111 例接受胃腺癌切除术患者肿瘤样本中 hENT 的免疫组织化学表达，将这些数据与临床参数和疾病结果相关联。所有患者在手术前后均未接受化疗或放疗作为辅助或新辅助方案的一部分。在单变量生存分析中，hENT1 的表达与总生存期（OS）和无病生存期（DFS）相关。具体来说，hENT1 过表达的患者 OS 更短（P=0.021），DFS 更短（P=0.033）。仅考虑淋巴结阳性患者，hENT 水平较高与中位 DFS 明显缩短相关（21.7 个月；95%CI 11.1-32.4），与 hENT1 低表达的患者相比。在淋巴结阳性患者中，hENT1 表达被定义为独立的预后因素（P=0.019）。此外，仅考虑弥漫性或混合性肿瘤和淋巴结阳性的患者，hENT1 的表达与 DFS 和 OS 密切相关。hENT1 蛋白的免疫组化在接受胃切除术的患者中具有预后信息，并有望成为化疗决策的预测因素。
