P53 and TLR4 expression are prognostic markers informing progression free survival of advanced stage high grade serous ovarian cancer

Objective: New prognostic biomarkers, and bio-signatures, are urgently needed to facilitate a precision medicine based approach to more effectively treat patients with high-grade serous ovarian cancer (HGSC). In this study, we analysed the expression patterns of a series of candidate protein biomarkers. Methods: The panel of markers which included MyD88, TLR4, MAD2, PR, OR, WT1, p53, p16, CD10 and Ki67 was assessed using immunohistochemistry in a tissue microarray (TMA) cohort of n = 80 patients, composed of stage 3-4 HGSCs. Each marker was analysed for their potential to predict both overall survival (OS) and progression free survival (PFS). Results: TLR4 and p53 were found to be individually predictive of poorer PFS (Log Rank, p = 0.017, p = 0.030 respectively). Cox regression analysis also identified high p53 and TLR4 expression as prognostic factors for reduced PFS (p53; HR=1.785, CI=1.036-3.074, p = 0.037 and TLR4; HR=2.175, CI=1.112-4.253, p = 0.023). Multivariate forward conditional Cox regression analysis, examining all markers, identified a combined signature composed of p53 and TLR4 as prognostic for reduced PFS (p = 0.023). Conclusion: Combined p53 and TLR4 marker assessment may help to aid treatment stratification for patients diagnosed with advanced-stage HGSC.