Background
Survival benefit from surgical debulking of ovarian cancer (OC) is well established but some women, despite total macroscopic clearance of disease, still have poor prognosis. We aimed to identify biomarkers to predict benefit from conventional surgery.
Methods
Clinical data from women debulked for high-stage OC was analysed (Hammersmith Hospital, London, UK; 2001-2014). Infinium’s HumanMethylation27 array interrogated tumour-DNA for differentially-methylated CpG sites, correlated to survival, in patients with the least residual disease (RD) (Hammersmith Array). Validation was performed using bisulphite pyrosequencing (Charité Hospital, Berlin, Germany cohort) and The Cancer Genome Atlas’ (TCGA) methylation dataset. Kaplan-Meier curves and Cox models tested survival.
Results
Altogether 803 women with serous ovarian cancer were studied. No RD was associated with significantly improved overall- (OS) (hazard ratio [HR] 1.25, 95% CI 1.06-1.47; P=0.0076) and progression-free survival (PFS) (HR 1.23, 1.05-1.43; P=0.012) (Hammersmith database n=430). Differentially-methylated loci within FGF4, FGF21, MYLK2, MYLK3, MYL7, and ITGAE associated with survival. Patients with the least RD had significantly better OS with higher methylation of MYLK3 (Hammersmith (HR 0.51, 0.31-0.84; P=0.01), Charité (0.46, 0.21-1.01; P=0.05), TCGA (0.64, 0.44-0.93; P=0.02)).
Conclusion
MYLK3 methylation is associated with improved OS in patients with the least RD, which could potentially be used to determine response to surgery.