Clinicopathological significance of ligase I, III & IV in Epithelial Ovarian Cancers


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M L Alabdullah1,A Alblihy2,R Ali3,P Moseley4,S Chan4,E Rakha2,S Madhusudan4
1university of nottingham,2University of Nottingham,3University of Nottigham,4Nottingham University Hospitals

Abstract

Background

Ligase I, III & IV join DNA breaks generated during replication and recombination in an ATP-dependent manner. Given the critical role in the maintenance of genomic integrity, we evaluated the clinical significance of ligase I, III & IV in epithelial ovarian cancers.

Method

Ligase I, III & IV expression in ovarian epithelial cancer was investigated in 525 ovarian cancer patients treated at Nottingham University Hospitals (NUH) between 1997 and 2010. Ligases expression was correlated with the clinicopathological features, recurrence free survival (RFS) and ovarian cancer specific survival (OCSS).

Results

High nuclear ligase I expression was significantly associated with serous type carcinoma (p < 0.0001), higher FIGO stage and tumour grade (p < 0.0001), non-optimal surgical tumour de-bulking (p = 0.004). High cytoplasmic ligase III was significantly associated with higher FIGO stage (p = 0.002), higher histology grade (p = 0.028), residual tumour following surgery (p = 0.001), measurable disease before chemotherapy (p= 0.006) and resistance to platinum chemotherapy (p = 0.025). On the other hand, high nuclear ligase IV expression was significantly associated with less residual tumour following surgical excision (p = 0.006) and better response to platinum based chemotherapy (p = 0.049). High ligase I and ligase III expressions were correlated with poor survival. However, high ligase IV was correlated with favourable outcome. In cox multivariate analysis ligase I expression was independently associated with poor outcome.

Conclusion

Human Ligases are promising predictive biomarkers in ovarian cancer. They have a vital role in platinum response and clinical outcome. Moreover, ligase I is a promising biomarker for stratification and personalization.