Predictive and prognostic value of human copper transporter 1 (hCtr1) in patients with stage III non-small-cell lung cancer receiving first-line platinum-based doublet chemotherapy

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• 作者：Helen H.W. Chen^a ; ^b ; Jiang-Jou Yan^c ; Wen-Chung Chen^c ; Macus Tien Kuo^d ; Yu-Hsuan Lai^b ; Wu-Wei Lai^e ; Hsiao-Sheng Liu^f ; ^g ; Wu-Chou Su^h ; ^{sunnysu@mail.ncku.edu.tw}
• 关键词：Human copper transporter 1 ; Cisplatin ; ATP7A ; ATP7B ; Non-small cell lung cancer ; Prognosis
• 刊名：Lung Cancer
• 出版年：2012
• 出版时间：February 2012
• 年：2012
• 卷：75
• 期：2
• 页码：228-234
• 全文大小：448 K

文摘

Background

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.

Methods

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.

Results

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).

Conclusion

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.