Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Lung Cancer. 2012 Feb;75(2):228-34. doi: 10.1016/j.lungcan.2011.06.011. Epub 2011 Jul 23.
Recent studies have shown that human copper transporter 1 (hCtr1), the major copper influx transporter, is involved in the transport of platinum-based antitumor agents. We investigated the predictive and prognostic values of hCtr1, and copper efflux transporters ATP7A and ATP7B, in patients with locally advanced non-small cell lung cancer (NSCLC) receiving first-line platinum-based chemotherapy.
From 2004 to 2009, we identified 54 consecutive stage III NSCLC patients who underwent first-line platinum-based doublet chemotherapy. Immunohistochemical studies of hCtr1, ATP7A and ATP7B on the paraffin-embedded pre-treatment tumor samples were performed and correlated with chemotherapy response and survival.
Overexpression of hCtr1, ATP7A and ATP7B were observed in 68%, 48% and 74% of the participants, respectively. hCtr1 overexpression was associated with better chemotherapy responses (P<0.01); whereas ATP7A and ATP7B were not. Patients with hCtr1 overexpressing tumors had better progression-free survival (PFS) and overall survival (OS) (P=0.01 and 0.047, respectively). In multivariate analyses for chemotherapy response and PFS, only hCtr1 overexpression emerged as a favorable independent predictive and prognostic factor (all P<0.01).
This is the first report to state that hCtr1 is not only an independent predictor of platinum-based chemotherapy response but also a prognostic factor in stage III NSCLC.
最近的研究表明，人类铜转运蛋白 1（hCtr1），主要的铜输入转运蛋白，参与铂类抗肿瘤药物的转运。我们研究了 hCtr1 以及铜输出转运蛋白 ATP7A 和 ATP7B 在接受一线铂类化疗的局部晚期非小细胞肺癌（NSCLC）患者中的预测和预后价值。
2004 年至 2009 年，我们鉴定了 54 例连续接受一线铂类双联化疗的 III 期 NSCLC 患者。对预处理肿瘤石蜡包埋标本进行 hCtr1、ATP7A 和 ATP7B 的免疫组织化学研究，并与化疗反应和生存相关联。
hCtr1、ATP7A 和 ATP7B 的过表达分别在 68%、48%和 74%的参与者中观察到。hCtr1 过表达与更好的化疗反应相关（P<0.01）；而 ATP7A 和 ATP7B 则不然。hCtr1 过表达肿瘤患者具有更好的无进展生存期（PFS）和总生存期（OS）（P=0.01 和 0.047）。在化疗反应和 PFS 的多变量分析中，只有 hCtr1 过表达是有利的独立预测和预后因素（均 P<0.01）。
这是第一项表明 hCtr1 不仅是铂类化疗反应的独立预测因子，而且是 III 期 NSCLC 的预后因素的报告。
