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

Pathol Res Pract. 2024 Jan:253:155020. doi: 10.1016/j.prp.2023.155020. Epub 2023 Dec 7.

Abstract

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.

Keywords: Biomarkers; Chemoresistance; Ovarian Cancer; P53; TLR4.

MeSH terms

  • Biomarkers
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Ovarian Epithelial
  • Cystadenocarcinoma, Serous* / metabolism
  • Female
  • Humans
  • Ovarian Neoplasms* / metabolism
  • Prognosis
  • Progression-Free Survival
  • Toll-Like Receptor 4 / metabolism
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Biomarkers
  • Biomarkers, Tumor
  • TLR4 protein, human
  • Toll-Like Receptor 4
  • Tumor Suppressor Protein p53
  • TP53 protein, human