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/m 2/day; days 1-14) and cisplatin (60 mg/m 2; 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.

Original languageEnglish
Pages (from-to)991-998
Number of pages8
JournalMedical Oncology
Volume28
Issue number4
DOIs
StatePublished - 1 Dec 2011

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Orotate Phosphoribosyltransferase
Cisplatin
Stomach Neoplasms
Biomarkers
Drug Therapy
Immunohistochemistry
Disease-Free Survival
Dihydrouracil Dehydrogenase (NADP)
Thymidine Phosphorylase
Fanconi Anemia
Thymidylate Synthase
Proteins
Survival
Glutathione Transferase
DNA Repair
Multivariate Analysis
X-Rays
Neoplasms

Keywords

  • Biomarker
  • Chemotherapy
  • Cisplatin
  • Gastric cancer
  • Orotate phosphoribosyltransferase
  • S-1

Cite this

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title = "Biomarker analysis in patients with advanced gastric cancer treated with S-1 plus cisplatin chemotherapy: Orotate phosphoribosyltransferase expression is associated with treatment outcomes",
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/m 2/day; days 1-14) and cisplatin (60 mg/m 2; 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.",
keywords = "Biomarker, Chemotherapy, Cisplatin, Gastric cancer, Orotate phosphoribosyltransferase, S-1",
author = "Choi, {In Sil} and Lee, {Hye Seung} and Lee, {Keun Wook} and Haeryoung Kim and Kim, {Ki Hwan} and Kim, {Yu Jung} and Kim, {Jee Hyun} and Kim, {Woo Ho} and Lee, {Jong Seok}",
year = "2011",
month = "12",
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doi = "10.1007/s12032-010-9590-4",
language = "English",
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T1 - Biomarker analysis in patients with advanced gastric cancer treated with S-1 plus cisplatin chemotherapy

T2 - Orotate phosphoribosyltransferase expression is associated with treatment outcomes

AU - Choi, In Sil

AU - Lee, Hye Seung

AU - Lee, Keun Wook

AU - Kim, Haeryoung

AU - Kim, Ki Hwan

AU - Kim, Yu Jung

AU - Kim, Jee Hyun

AU - Kim, Woo Ho

AU - Lee, Jong Seok

PY - 2011/12/1

Y1 - 2011/12/1

N2 - 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/m 2/day; days 1-14) and cisplatin (60 mg/m 2; 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.

AB - 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/m 2/day; days 1-14) and cisplatin (60 mg/m 2; 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.

KW - Biomarker

KW - Chemotherapy

KW - Cisplatin

KW - Gastric cancer

KW - Orotate phosphoribosyltransferase

KW - S-1

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DO - 10.1007/s12032-010-9590-4

M3 - Article

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JO - Medical Oncology

JF - Medical Oncology

SN - 1357-0560

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