Expression of Topoisomerase 1 and carboxylesterase 2 correlates with irinotecan treatment response in metastatic colorectal cancer
Open accessAbstract
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.
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CES2 expression in CRC is positively correlated with irinotecan sensitivity.
“Multiple studies have shown that the expression of CES2 in CRC is positively correlated with irinotecan sensitivity [89,90].”
From Drug Resistance in Colorectal Cancer: From Mechanism to Clinic (2022) · cites this paper as [89]
Mutations or lower expression of TOP-1 may cause irinotecan resistance in CRC.
“Given the targeting properties of irinotecan or its active metabolite SN-38, mutations or lower expression of TOP-1 may cause irinotecan resistance to CRC [89].”
From Drug Resistance in Colorectal Cancer: From Mechanism to Clinic (2022) · cites this paper as [89]
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- Authors
- Shaojun, C., Li, H., Haixin, H., & Guisheng, L.
- Affiliations
- The Fourth Affiliated Hospital of Guangxi Medical University
- Fourth Affiliated Hospital of Guangxi Medical University (CN)
- ORCID
- Li, Hua
- Venue
- Cancer Biology & Therapy
- Publisher
- Informa UK Limited
- Published
- 2018-01-16
- Volume
- 19
- Issue
- 3
- Pages
- 153-159
- ISSN
- 1538-4047 (ISSN-L)
- 1555-8576
- PMC
- PMC5790385
- OpenAlex
- W2776794398
- Cited by
- 54
- References
- 24
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 8 · 2023: 3 · 2022: 15 · 2021: 8 · 2020: 6 · 2019: 5 · 2018: 1
- FWCI
- 1.34
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cancer Biology & Therapy (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81260340)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer therapeutics and mechanisms
- Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Keywords
- topoisomerase I, CE2, irinotecan, metastatic colorectal cancer, chemotherapy response, prognostic factors, progression-free survival, overall survival
- MeSH terms
- Irinotecan, Oxaliplatin, Progression-Free Survival, Antineoplastic Combined Chemotherapy Protocols, Leucovorin, DNA Topoisomerases, Type I, Drug Combinations, Female, Fluorouracil, Follow-Up Studies, Humans, Male, Middle Aged, Organometallic Compounds, Prognosis, Colorectal Neoplasms, Gene Expression Regulation, Neoplastic, Carboxylesterase, Kaplan-Meier Estimate, Topoisomerase I Inhibitors
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