High APOBEC3B expression is a predictor of recurrence in patients with low-risk clear cell renal cell carcinoma

Urol Oncol. 2015 Aug;33(8):340.e1-8. doi: 10.1016/j.urolonc.2015.05.009. Epub 2015 Jun 4.

Abstract

Purpose: APOBEC3B is a member of the cytosine deaminase family, which converts cytosine to uracil during RNA editing and retrovirus or retrotransposon restriction. Recent evidence has revealed that APOBEC3B-catalyzed genomic DNA deamination could provide genetic fuel for cancer development, metastasis, and even treatment resistance. The aim of this study was to assess the association between APOBEC3B expression and the risk of recurrence after surgery in patients with renal cell carcinoma (RCC).

Methods: We retrospectively enrolled 299 consecutive patients with RCC who underwent nephrectomy at a single center in 2008. Clinicopathologic variables and recurrence-free survival (RFS) were recorded. APOBEC3B expression levels were determined by immunohistochemistry in tumor tissues. Kaplan-Meier method was applied to compare survival curves. Cox regression models were fitted to analyze the effect of prognostic factors on RFS. The Harrell concordance index was calculated to assess predictive accuracy.

Results: High APOBEC3B expression was associated with an increased risk of recurrence in patients with clear cell RCC (ccRCC) (P<0.001) rather than in patients with non-ccRCC (P = 0.247). After backward elimination, APOBEC3B expression was identified as an independent prognostic factor for RFS in patients with clear cell histology (P = 0.016). The predictive accuracy of the Leibovich prognostic score was improved when APOBEC3B expression was incorporated. Notably, the improvement in prediction mainly took place in patients with low-risk disease defined by the Leibovich score.

Conclusions: High APOBEC3B expression is an independent predictor of recurrence in patients with ccRCC, and the prognostic value is most prominent in those with low-risk disease.

Keywords: APOBEC3B; Prognostic biomarker; Recurrence-free survival; Renal cell carcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Carcinoma, Renal Cell / genetics*
  • Carcinoma, Renal Cell / metabolism*
  • Carcinoma, Renal Cell / mortality
  • Carcinoma, Renal Cell / pathology
  • Cytidine Deaminase / metabolism*
  • Female
  • Humans
  • Kidney Neoplasms / genetics*
  • Kidney Neoplasms / metabolism*
  • Kidney Neoplasms / mortality
  • Kidney Neoplasms / pathology
  • Male
  • Middle Aged
  • Minor Histocompatibility Antigens
  • Neoplasm Recurrence, Local
  • Prognosis
  • Retrospective Studies
  • Risk Factors

Substances

  • Minor Histocompatibility Antigens
  • APOBEC3B protein, human
  • Cytidine Deaminase

Supplementary concepts

  • Clear-cell metastatic renal cell carcinoma