Background:
Copper transporter 1 (CTR1) is a critical determinant of the uptake and cytotoxic effect of the
platinum drugs
carboplatin and
cisplatin.
Thymidylate synthase (TS) is an
enzyme involved in
DNA synthesis and is associated with resistance of
tumor cells to
5-fluorouracil. We investigated the correlation between CTR1 and TS expression levels and treatment outcomes in patients with advanced
non-small-cell lung cancer (NSCLC) treated with S-1/
carboplatin doublet
chemotherapy. Methods: Twenty-nine patients were enrolled in this study.
Tumor expression of CTR1 and TS was measured immunohistochemically and analyzed for correlation with
tumor response, progression-free survival (PFS), and overall survival (OS). Results:
Tumor response was significantly better in patients with CTR1High
tumors than in patients with CTR1Low
tumors (64% vs. 18%, P = 0.02). Patients with TSLow
tumors had a significantly longer OS (median 21.2 vs. 8.5 months, P = 0.02), but not PFS, than patients with TSHigh
tumors. When CTR1 and TS co-expression was analyzed, patients with either CTR1High or TSLow
tumors showed a significantly better
tumor response (50% vs. 0%, P = 0.01), longer PFS (median 4.2 vs. 2.1 months, P = 0.03), and longer OS (median 21.2 vs. 8.5 months, P = 0.01) than patients with both CTR1Low and TSHigh
tumors. Conclusions: Our study suggests that combined CTR1/TS expression status has the potential to be an important predictor of good treatment outcomes in patients with advanced NSCLC treated with S-1/
carboplatin doublet
chemotherapy.