Targeting of topoisomerases for prognosis and drug resistance in ovarian cancer.
BACKGROUND
As magicians of the DNA world, topoisomerases resolve all of the topological problems in relation to DNA during a variety of genetic processes. While the prognostic value of topoisomerase isoenzymes in epithelial ovarian carcinoma (EOC) is still elusive. In current study, we investigated the prognostic value of topoisomerase isoenzymes in the EOC patients. Kaplan Meier plotter (KM plotter) database were used to assess the relevance of individual topoisomerase isoenzyme mRNA expression to EOC patients overall survival (OS), in which updated survival information and gene expression data were from a total of 1,648 EOC patients.


RESULTS
High expression of TOP1 and TOP2A were found to be correlated to worse OS in all patients and serous patients, but not in endometrioid patients. Contrary to TOP1 and TOP2A, TOP3A and TOP3B expression were associated with better OS in all patients and serous patients, but not in endometrioid patients. While TOP2B were not found any significant prognostic value for EOC patients. From the Oncomine database, we also found widespread upregulation in the expression of TOP1 and TOP2A genes in primary tumor tissues. Albeit limited in number, all datasets exhibiting differential expression showed TOP3A and TOP3B under-regulated.


CONCLUSIONS
These results strongly supported that TOP1 and TOP2A were potential biomarkers for predicting poor survival of EOC patients, while TOP3A and TOP3B were expected to be further exploited as tumor suppressors. Comprehensive understanding of the topoisomerase isoforms may have guiding significance for the diagnosis treatment and prognosis in EOC patients.
Obstetrics and Gynecology Hospital, Fudan University, Shanghai, 200011, China.|Department of Obstetrics and Gynecology of Shanghai Medical College, Fudan University, Shanghai, 200032, China.|Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai, 200011, China.
Yang
Y
Bai
Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai, 200030, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200030, China.
Liang-Dong
LD
Li
Obstetrics and Gynecology Hospital, Fudan University, Shanghai, 200011, China.|Department of Obstetrics and Gynecology of Shanghai Medical College, Fudan University, Shanghai, 200032, China.|Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai, 200011, China.
Jun
J
Li
Obstetrics and Gynecology Hospital, Fudan University, Shanghai, 200011, China. 052108365@fudan.edu.cn.|Department of Obstetrics and Gynecology of Shanghai Medical College, Fudan University, Shanghai, 200032, China. 052108365@fudan.edu.cn.|Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai, 200011, China. 052108365@fudan.edu.cn.|Permanent address: Department of Gynecology, Obstetrics and Gynecology Hospital of Fudan University, No.419, Fangxie Road, Shanghai, 200011, China. 052108365@fudan.edu.cn.
Xin
X
Lu
D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D014408:Biomarkers, Tumor; D016000:Cluster Analysis; D019295:Computational Biology / Q000379:methods; D026942:DNA Topoisomerases / Q000235:genetics* / Q000378:metabolism; D030561:Databases, Nucleic Acid; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007527:Isoenzymes; D053208:Kaplan-Meier Estimate; D005810:Multigene Family; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D011379:Prognosis; D059003:Topoisomerase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D007527:Isoenzymes; D059003:Topoisomerase Inhibitors; D026942:DNA Topoisomerases
Epithelial ovarian cancer (EOC); Kaplan Meier plotter; Oncomine; Prognosis; Topoisomerases