Expression of p52, a non-canonical NF-kappaB transcription factor, is associated with poor ovarian cancer prognosis.

Background: The canonical and non-canonical nuclear factor-kappaB (NF-κB) signaling pathways have key roles in cancer, but studies have previously evaluated only the association of canonical transcription factors and ovarian cancer survival. Although a number of in vitro and in vivo studies have demonstrated mechanisms by which non-canonical NF-κB signaling potentially contributes to ovarian cancer progression, a prognostic association has yet to be shown in the clinical context.
Methods: We assayed p65 and p52 (major components of the canonical and non-canonical NF-κB pathways) by immunohistochemistry in epithelial ovarian tumor samples; nuclear and cytoplasmic staining were semi-quantified by H-scores and dichotomized at median values. Associations of p65 and p52 with progression-free survival (PFS) and overall survival (OS) were quantified by Hazard Ratios (HR) from proportional-hazards regression.
Results: Among 196 cases, median p52 and p65 H-scores were higher in high-grade serous cancers. Multivariable regression models indicated that higher p52 was associated with higher hazards of disease progression (cytoplasmic HR: 1.54; nuclear HR: 1.67) and death (cytoplasmic HR: 1.53; nuclear HR: 1.49), while higher nuclear p65 was associated with only a higher hazard of disease progression (HR: 1.40) in unadjusted models. When cytoplasmic and nuclear staining were combined, p52 remained significantly associated with increased hazards of disease progression (HR: 1.91, p  = 0.004) and death (HR: 1.70, p  = 0.021), even after adjustment for p65 and in analyses among only high-grade serous tumors.
Conclusions: This is the first study to demonstrate that p52, a major component of non-canonical NF-κB signaling, may be an independent prognostic factor for epithelial ovarian cancer, particularly high-grade serous ovarian cancer. Approaches to inhibit non-canonical NF-κB signaling should be explored as novel ovarian cancer therapies are needed.
Competing Interests: Competing interestsThe authors declare that they have no competing interests. However, potential conflicts of interest may include the following: ABF reports reimbursement for committee service from the American College of Obstetricians and Gynecologists (ACOG); MAC reports grants and personal fees from Astra-Zeneca, grants from Tesaro, grants from Janssen Research and Development, grants from Leap Therapeutics, grants from Aprea Therapeutics, grants from Advaxis, and grants from Hoffman-LaRoche; and TSB reports grants from Boehringer Ingelheim and grants from Celgene.
(© The Author(s) 2020.)