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

Abstract

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.

Fig. 1

Immunohistochemical stains for hCtr1 in representive non-small-cell lung carcinomas. (A) Carcinoma cells showing htCr1 overexpression manifested by diffuse cytoplasmic staining of strong intensity (200×). (B) Carcinoma cells showing low hCtr1 immunostaining activity (200×).

Fig. 2

Progression-free survival (PFS) curves in non-small-cell Lung carcinoma patients with hCtr1 overexpression tumors and hCtr1 low expression tumors (A). ATP7A overexpression tumors and ATP7A low expression tumors (B). ATP7B overexpression tumors and ATP7B low expression tumors (C).

Fig. 3

Overall survival (OS) curves in non-small-cell lung carcinoma patients with hCtr1 overexpression tumors and hCtr1 low expression tumors (A), ATP7A overexpression tumors and ATP7A low expression tumors (B). ATP7B overexpression tumors and ATP7B low expression tumors (C).