The Prognostic Role of the Non-Canonical Nuclear Factor-Kappa B Pathway in Renal Cell Carcinoma Patients

Urol Int. 2018;101(2):190-196. doi: 10.1159/000489816. Epub 2018 Aug 8.

Abstract

Background: In the United Kingdom, 8,000 cases of renal cancer are diagnosed each year, with a 5-year survival rate of 50%. Treatment options are limited; a potential therapeutic target is the non-canonical nuclear factor-kappa B (NF-κB) pathway. This pathway plays a role in multiple oncogenic processes in solid tumors. The aim of this study was to investigate the non-canonical nuclear factor pathway in renal cell carcinoma (RCC).

Materials and methods: NIK, IKKα, and RelB were investigated via immunohistochemistry in a cohort of 192 patients with clear cell renal cancer.

Results: High cytoplasmic NIK was associated with poorer cancer-specific survival (p = 0.006) and 10-year survival stratified from 85% (low) to 65% (high, p = 0.005). Similarly, high cytoplasmic RelB was associated with poorer cancer-specific survival (p = 0.041) and 10-year survival stratified from 88% (low) to 73% (high, p = 0.030). When clinicopathological characteristics were assessed, cytoplasmic NIK was associated with survival (p = 0.014), whereas cytoplasmic RelB was associated with increased tumor grade (p = 0.020) and decreased inflammation (p = 0.019). Upon multivariate analysis, it was found that cytoplasmic NIK was independently associated with cancer-specific survival (p = 0.009).

Conclusions: The non-canonical NF-κB pathway is associated with poorer cancer-specific survival in RCC patients, making it a viable target for therapeutic intervention. Furthermore, cytoplasmic NIK is a potential prognostic biomarker for this disease.

Keywords: Biomarkers; Carcinoma; Inflammation; Nuclear factor-kappa B; Renal cell.

MeSH terms

  • Biomarkers, Tumor / analysis*
  • Carcinoma, Renal Cell / chemistry*
  • Carcinoma, Renal Cell / mortality
  • Carcinoma, Renal Cell / pathology
  • Carcinoma, Renal Cell / surgery
  • Female
  • Humans
  • I-kappa B Kinase / analysis*
  • Immunohistochemistry
  • Kidney Neoplasms / chemistry*
  • Kidney Neoplasms / mortality
  • Kidney Neoplasms / pathology
  • Kidney Neoplasms / surgery
  • Male
  • Middle Aged
  • NF-kappaB-Inducing Kinase
  • Neoplasm Grading
  • Neoplasm Staging
  • Nephrectomy
  • Progression-Free Survival
  • Protein Serine-Threonine Kinases / analysis*
  • Risk Factors
  • Time Factors
  • Transcription Factor RelB / analysis*
  • Treatment Outcome

Substances

  • Biomarkers, Tumor
  • RELB protein, human
  • Transcription Factor RelB
  • Protein Serine-Threonine Kinases
  • CHUK protein, human
  • I-kappa B Kinase