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

被引:35
作者
Chen Shaojun [1 ]
Hua Li [1 ]
Huang Haixin [1 ]
Li Guisheng [1 ]
机构
[1] Guangxi Med Univ, Affiliated Hosp 4, Dept Med Oncol, Liuzhou, Guangxi, Peoples R China
基金
中国国家自然科学基金;
关键词
TOPO-1; CES-2; colorectal cancer; irinotecan; chemotherapy; PFS; OS; FLUOROURACIL; CHEMOTHERAPY; ANTICANCER; CES2;
D O I
10.1080/15384047.2017.1414754
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:153 / 159
页数:7
相关论文
共 29 条
[1]   Role of topoisomerase I and thymidylate synthase expression in sporadic colorectal cancer: Associations with clinicopathological and molecular features [J].
Azzoni, Cinzia ;
Bottarelli, Lorena ;
Cecchini, Stefano ;
Ziccarelli, Antonio ;
Campanini, Nicoletta ;
Bordi, Cesare ;
Sarli, Leopoldo ;
Silini, Enrico Maria .
PATHOLOGY RESEARCH AND PRACTICE, 2014, 210 (02) :111-117
[2]  
Bar JK, 2012, ADV CLIN EXP MED, V21, P35
[3]   Predictive biomarkers of chemotherapy efficacy in colorectal cancer: Results from the UK MRC FOCUS trial [J].
Braun, Michael S. ;
Richman, Susan D. ;
Quirke, Philip ;
Daly, Catherine ;
Adlard, Julian W. ;
Elliott, Faye ;
Barrett, Jennifer H. ;
Selby, Peter ;
Meade, Angela M. ;
Stephens, Richard J. ;
Parmar, Mahesh K. B. ;
Seymour, Matthew T. .
JOURNAL OF CLINICAL ONCOLOGY, 2008, 26 (16) :2690-2698
[4]   Carboxylesterase 2 as a Determinant of Response to Irinotecan and Neoadjuvant FOLFIRINOX Therapy in Pancreatic Ductal Adenocarcinoma [J].
Capello, Michela ;
Lee, Minhee ;
Wang, Hong ;
Babel, Ingrid ;
Katz, Matthew H. ;
Fleming, Jason B. ;
Maitra, Anirban ;
Wang, Huamin ;
Tian, Weihua ;
Taguchi, Ayumu ;
Hanash, Samir M. .
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, 2015, 107 (08)
[5]   Response Rates of Hepatic Arterial Infusion Pump Therapy in Patients With Metastatic Colorectal Cancer Liver Metastases Refractory to All Standard Chemotherapies [J].
Cercek, Andrea ;
Boucher, Taryn M. ;
Gluskin, Jill S. ;
Aguilo, Ariel ;
Chou, Joanne F. ;
Connell, Louise C. ;
Capanu, Marinela ;
Reidy-Lagunes, Diane ;
D'Angelica, Michael ;
Kemeny, Nancy E. .
JOURNAL OF SURGICAL ONCOLOGY, 2016, 114 (06) :655-663
[6]   Molecular Diagnostics for Precision Medicine in Colorectal Cancer: Current Status and Future Perspective [J].
Chen, Guoli ;
Yang, Zhaohai ;
Eshleman, James R. ;
Netto, George J. ;
Lin, Ming-Tseh .
BIOMED RESEARCH INTERNATIONAL, 2016, 2016
[7]   Attenuation of cytogenetic effects by erythropoietin in human lymphocytes in vitro and P388 ascites tumor cells in vivo treated with irinotecan (CPT-11) [J].
Digkas, E. ;
Kareli, D. ;
Chrisafi, S. ;
Passadaki, T. ;
Mantadakis, E. ;
Hatzimichail, A. ;
Vargemezis, V. ;
Lialiaris, Th. .
FOOD AND CHEMICAL TOXICOLOGY, 2010, 48 (01) :242-249
[8]   Irinotecan combined with fluorouracil compared with fluorouracil alone as first-line treatment for metastatic colorectal cancer: a multicentre randomised trial [J].
Douillard, JY ;
Cunningham, D ;
Roth, AD ;
Navarro, M ;
James, RD ;
Karasek, P ;
Jandik, P ;
Iveson, T ;
Carmichael, J ;
Alakl, M ;
Gruia, G ;
Awad, L ;
Rougier, P .
LANCET, 2000, 355 (9209) :1041-1047
[9]   Irinotecan, a key chemotherapeutic drug for metastatic colorectal cancer [J].
Fujita, Ken-ichi ;
Kubota, Yutaro ;
Ishida, Hiroo ;
Sasaki, Yasutsuna .
WORLD JOURNAL OF GASTROENTEROLOGY, 2015, 21 (43) :12234-12248
[10]   Organ-specific carboxylesterase profiling identifies the small intestine and kidney as major contributors of activation of the anticancer prodrug CPT-11 [J].
Hatfield, M. Jason ;
Tsurkan, Lyudmila ;
Garrett, Michael ;
Shaver, Timothy M. ;
Hyatt, Janice L. ;
Edwards, Carol C. ;
Hicks, Latorya D. ;
Potter, Philip M. .
BIOCHEMICAL PHARMACOLOGY, 2011, 81 (01) :24-31