Alabdullah ML1,2*, Miligy I1,3, Alblihy A1, Ali R1, Toss M1, Chan S1, Madhusudan S1,4 and Rakha EA1
1Division of Cancer and Stem Cells, University of Nottingham Biodiscovery Institute, UK
2Department of Pediatric Surgery, Leicester University Teaching Hospitals NHS Trust, UK
3Department of Pathology, Menoufia University, Egypt
4Department of Oncology, Nottingham University Hospitals, UK
Background: DNA Damage Repair (DDR) proteins have crucial roles and can modify tumor behavior. XRCC1, PARP1 and polβ are important driving biomarkers that could enhance OC development and progression. They are key proteins in DDR. Although different studies have investigated their role in different cancerous organs, there remains a lack of knowledge on how the interaction between these proteins can influence the ovarian tumor cases. This study evaluates the biological and prognostic significance of the above proteins, in addition, to identify the one that has the dominating function in primary OC patients.
Methods: PARP1, XRCC1 and polβ expression was assessed immunohistochemically in a large primary OC cohort (n=525). Outcome analysis was evaluated using Progression Free (PFS) and Overall Survival (OS).
Results: High PARP1and XRCC1 expression was associated with features of high risk OC, including serous histology, advanced grade/stage, and higher residual tumor following surgery. Similarly, polβ overexpression was linked to serous histology and higher stage tumors. On the other hand, XRCC1 negative/low expression improved patients’ platinum sensitivity. Interestingly, overexpression of all the surrogate biomarkers was associated with poor outcome, not just in the whole cohort but also in platinum sensitive tumors. Importantly, the multivariate analysis revealed that XRCC1 is an independent factor for poor PFS and PARP1 for OS.
Conclusion: The DDR proteins (PARP1, XRCC1 and polβ) have crucial roles in OC progression and can potentially predict patients’ outcome. The data presented here reveal a novel network between the investigated proteins with vital clinical applications in OC. Therefore, this current study highlighted the critical role of this network, which could be utilized as a future therapeutic target in primary OC.
DNA Repair; XRCC1; PARP1; polβ; Ovarian cancer; Prognosis
Alabdullah ML, Miligy I, Alblihy A, Ali R, Toss M, Chan S, Madhusudan S, et al. DNA Damage Repair Proteins (PARP1, XRCC1 and POLβ) have Unfavorable Potential Prognostic Role in Primary Ovarian Cancer. Clin Oncol. 2021;6:1869..