Correlation of Apobec Mrna Expression with overall Survival and pd-l1 Expression in Urothelial Carcinoma

Sci Rep. 2016 Jun 10:6:27702. doi: 10.1038/srep27702.

Abstract

Metastatic urothelial carcinoma (mUC) has a very high mutational rate and is associated with an APOBEC mutation signature. We examined the correlation of APOBEC expression with overall survival (OS) and PD-L1 expression in a cohort of 73 mUC patients. mRNA expression of APOBEC3 family of genes (A3A, A3B, A3C, A3F_a, A3F_b, A3G, A3H) was measured using Nanostring. PD-L1 expression, evaluated by immunohistochemistry, on tumor infiltrating mononuclear cells (TIMCs) and tumor cells was scored from 0 to 4, with 2-4 being positive. Wilcoxon's non-parametric tests assessed the association of APOBEC and PD-L1. The Cox regression model assessed the association of APOBEC with OS. All APOBEC genes were expressed in mUC. Increased A3A, A3D, and A3H expression associates with PD-L1 positive TIMCs (p = 0.0009, 0.009, 0.06). Decreased A3B expression was marginally associated with PD-L1 positive TIMCs expression (p = 0.05). Increased A3F_a and A3F_b expression was associated with increased expression of PD-L1 on tumor cells (p = 0.05). Increased expression of A3D and A3H was associated with longer OS (p = 0.0009). Specific APOBEC genes have different effects on mUC in terms of survival and PD-L1 expression. A3D and A3H may have the most important role in mUC as they are associated with OS and PD-L1 TIMC expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • APOBEC Deaminases
  • B7-H1 Antigen / genetics*
  • B7-H1 Antigen / metabolism
  • Cell Line, Tumor
  • Cytidine Deaminase
  • Cytosine Deaminase / genetics*
  • Cytosine Deaminase / metabolism
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Survival Analysis
  • Urinary Bladder Neoplasms / genetics*
  • Urinary Bladder Neoplasms / pathology
  • Urothelium / metabolism
  • Urothelium / pathology*

Substances

  • B7-H1 Antigen
  • CD274 protein, human
  • RNA, Messenger
  • Cytosine Deaminase
  • APOBEC Deaminases
  • APOBEC3 proteins, human
  • Cytidine Deaminase