Orotate phosphoribosyltransferase as a predictor of benefit from S-1 adjuvant chemotherapy for cholangiocarcinoma patients

J Gastroenterol Hepatol. 2019 Jun;34(6):1108-1115. doi: 10.1111/jgh.14477. Epub 2018 Oct 19.

Abstract

Background and aim: To improve the prognosis of cholangiocarcinoma, we investigated potential biomarkers that may enable the selection of patients for whom postoperative adjuvant chemotherapy is likely effective.

Methods: The cohort of this retrospective study included 170 surgically resected cholangiocarcinoma patients, 26 with gemcitabine adjuvant chemotherapy (GEM group), 36 with S-1 adjuvant chemotherapy (S-1 group), and 103 receiving no adjuvant chemotherapy (NC group). Propensity score matching was performed to adjust patient backgrounds; 36 patients from the NC group then were selected. Immunohistochemistry of orotate phosphoribosyltransferase (OPRT) and human equilibrative nucleoside transporter 1 (hENT1) was performed to determine the correlation between their expression and disease-free survival (DFS).

Results: After matching, the backgrounds of these three groups were unbiased. No significant improvement of DFS by adjuvant chemotherapy was observed in the whole cohort. However, among the high-OPRT-expression patients, DFS of GEM, S-1, and NC groups at 5 years was 28.8%, 53.8%, and 25.5%, respectively. The DFS of the S-1 group was significantly longer than that of the NC group (P = 0.034). On the other hand, no significant differences in DFS were observed among the low OPRT expression patients. hENT1 expression was shown to have no predictive value. Multivariate analysis of the high-OPRT-expression patients demonstrated that S-1 adjuvant chemotherapy can reduce tumor recurrence (HR, 0.303; P = 0.013).

Conclusion: Cholangiocarcinoma patients with high OPRT expression would benefit from postoperative adjuvant S-1 therapy, which increases the DFS. Assessment of OPRT expression may contribute to the optimization of adjuvant chemotherapy for cholangiocarcinoma.

Keywords: OPRT; S-1; adjuvant chemotherapy; cholangiocarcinoma; oral fluoropyrimidine.

MeSH terms

  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bile Duct Neoplasms / diagnosis*
  • Bile Duct Neoplasms / drug therapy*
  • Bile Duct Neoplasms / mortality
  • Bile Duct Neoplasms / surgery
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Chemotherapy, Adjuvant*
  • Cholangiocarcinoma / diagnosis*
  • Cholangiocarcinoma / drug therapy*
  • Cholangiocarcinoma / mortality
  • Cholangiocarcinoma / surgery
  • Cohort Studies
  • Drug Combinations
  • Equilibrative Nucleoside Transporter 1 / genetics
  • Equilibrative Nucleoside Transporter 1 / metabolism
  • Female
  • Gene Expression
  • Humans
  • Immunohistochemistry
  • Male
  • Orotate Phosphoribosyltransferase / genetics
  • Orotate Phosphoribosyltransferase / metabolism*
  • Oxonic Acid / administration & dosage*
  • Predictive Value of Tests
  • Retrospective Studies
  • Survival Rate
  • Tegafur / administration & dosage*
  • Treatment Outcome

Substances

  • Biomarkers, Tumor
  • Drug Combinations
  • Equilibrative Nucleoside Transporter 1
  • SLC29A1 protein, human
  • S 1 (combination)
  • Tegafur
  • Oxonic Acid
  • Orotate Phosphoribosyltransferase