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Biomarker analysis in patients with advanced gastric cancer treated with S-1 plus cisplatin chemotherapy: orotate phosphoribosyltransferase expression is associated with treatment outcomes

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Abstract

This study was performed to analyze the impact of protein expression related to fluoropyrimidine and cisplatin metabolism (thymidylate synthase, dihydropyrimidine dehydrogenase, thymidine phosphorylase, orotate phosphoribosyltransferase [OPRT], excision repair cross-complementation 1, Fanconi anemia complementation group D2, glutathione S-transferase P1, and X-ray repair cross-complementing group 1) on treatment outcomes in patients with metastatic or relapsed gastric cancer (MRGC) receiving S-1/cisplatin chemotherapy. Protein expression was measured by immunohistochemistry (IHC). Of the 43 patients who had received S-1 (80 mg/m2/day; days 1–14) and cisplatin (60 mg/m2; day 1) every 3 weeks and had available tissue blocks, IHC was successfully performed in 41 patients. Patients with high OPRT levels in tumor tissues (IHC score ≥6) had superior progression-free survival (PFS) (23.3 vs. 14.1 weeks [median]) and overall survival (OS) (72.4 vs. 55.4 weeks [median]) to those with low OPRT levels (IHC score ≤5; P-values <.05). Expression levels of other proteins were not predictive of treatment outcomes. In multivariate analysis, both a good performance status and a high OPRT level were independently associated with prolonged PFS and OS. The OPRT expression level may be a good predictive marker in S-1/cisplatin-treated patients with MRGC.

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Acknowledgments

This study was partially supported by grants from Korean Cancer Research Foundation, Seoul National University Bundang Hospital Research Fund (11-2008-034), and Seoul Municipal Boramae Hospital Clinical Research Fund.

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Authors and Affiliations

  1. Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, 300 Gumi-dong, Bundang-gu, Seongnam-si, Gyeongi-do, 463-707, Korea

    Keun-Wook Lee, Ki Hwan Kim, Yu Jung Kim, Jee Hyun Kim & Jong Seok Lee

  2. Department of Pathology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea

    Hye Seung Lee & Haeryoung Kim

  3. Department of Internal Medicine, Seoul Municipal Boramae Hospital, Seoul National University College of Medicine, Seoul, Korea

    In Sil Choi

  4. Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea

    Woo Ho Kim

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  1. In Sil Choi
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Correspondence to Keun-Wook Lee.

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The authors In Sil Choi and Hye Seung Lee contributed equally to this work.

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Choi, I.S., Lee, H.S., Lee, KW. et al. Biomarker analysis in patients with advanced gastric cancer treated with S-1 plus cisplatin chemotherapy: orotate phosphoribosyltransferase expression is associated with treatment outcomes. Med Oncol 28, 991–998 (2011). https://doi.org/10.1007/s12032-010-9590-4

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  • DOI: https://doi.org/10.1007/s12032-010-9590-4

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