Correlation of Expression Levels of Copper Transporter 1 and Thymidylate Synthase with Treatment Outcomes in Patients with Advanced Non-small Cell Lung Cancer Treated with S-1/Carboplatin Doublet Chemotherapy

Document Type: Research Articles

Authors

1 Laboratory of Pathology, Department of Medical Biophysics, Kobe University Graduate School of Health Sciences, 7-10-2 Tomogaoka, Suma, Kobe, Hyogo, Japan.

2 Department of Respiratory Medicine, Japanese Red Cross Kobe Hospital, 1-3-1 Wakihama-kaigandori, Chuo, Kobe, Hyogo, Japan.

3 Department of Medical Oncology, Kobe City Medical Center General Hospital, 2-2 Minatojima Minamimachi, Chuo, Kobe, Hyogo, Japan.

4 Department of Diagnostic Pathology, Kobe City Medical Center General Hospital, 2-2 Minatojima Minamimachi, Chuo, Kobe, Hyogo, Japan.

Abstract

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.

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