Expression of Topoisomerase 1 and carboxylesterase 2 correlates with irinotecan treatment response in metastatic colorectal cancer

Cancer Biol Ther. 2018 Mar 4;19(3):153-159. doi: 10.1080/15384047.2017.1414754. Epub 2018 Jan 16.

Abstract

Topoisomerase 1 (TOPO-1) and carboxylesterase 2 (CES-2) are found to play crucial roles in the pathogenesis of various cancers. The prognostic role of TOPO-1 and CES-2 in patients with metastatic colorectal cancer (mCRC) who underwent irinotecan chemotherapy was largely unknown. In the current study, we assessed the expression of TOPO-1 and CES-2 in mCRC and analyzed its potential relevance to irinotecan based therapy. A total of 98 patients with mCRC were included in this study. The expression of TOPO-1 and CES-2 in mCRC tissues was evaluated by immunohistochemistry. For TOPO-1, 46 patients showed high expression and 52 patients showed low expression. For CES-2, 53 patients showed high expression and 45 patients showed low expression. The correlation between TOPO-1 or CES-2 expression and clinicopathological characteristics of mCRC patients was analyzed. Neither TOPO-1 nor CES-2 had significant correlation with age, gender, tumor site, tumor grade and metastatic sites in mCRC patients. However, high expression of CES-2 but not TOP-1 was positively correlated with better curative effect. Kaplan-Meier and log-rank test were applied to assess the correlation between progression-free survival (PFS)/overall survival (OS) and TOPO-1 or CES-2 expression in mCRC patients. High expression of TOPO-1 and CES-2 are correlated with longer PFS and OS. In summary, our findings suggest that TOPO-1 and CES-2 may play important roles irinotecan sensitivity in mCRC patients. Evaluation of expression of TOPO-1 and CES-2 may provide preliminary clinical evidence for the management of irinotecan-based therapy in mCRC patients.

Keywords: CES-2; OS; PFS; TOPO-1; chemotherapy; colorectal cancer; irinotecan.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carboxylesterase / metabolism*
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology
  • DNA Topoisomerases, Type I / metabolism*
  • Drug Combinations
  • Female
  • Fluorouracil / therapeutic use*
  • Follow-Up Studies
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Irinotecan
  • Kaplan-Meier Estimate
  • Leucovorin / therapeutic use*
  • Male
  • Middle Aged
  • Organometallic Compounds / therapeutic use*
  • Oxaliplatin
  • Prognosis
  • Progression-Free Survival
  • Topoisomerase I Inhibitors / therapeutic use*

Substances

  • Drug Combinations
  • Organometallic Compounds
  • Topoisomerase I Inhibitors
  • folfirinox
  • Oxaliplatin
  • Irinotecan
  • CES2 protein, human
  • Carboxylesterase
  • DNA Topoisomerases, Type I
  • TOP1 protein, human
  • Leucovorin
  • Fluorouracil

Grants and funding

National Natural Science Foundation of China (NSFC); 81260340.