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

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.

• Authors: Chen Shaojun, Hua Li, Huang Haixin, Li Guisheng
• Journal: Cancer biology & therapy (Cancer Biol Ther) Vol. 19 Issue 3 Pg. 153-159 (03 04 2018) ISSN: 1555-8576 [Electronic] United States
• PMID: 29261002 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Carboxylesterase (metabolism)
• Colorectal Neoplasms (drug therapy, genetics, mortality, 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)