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

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.

• Authors: Stephanie A Mullane, Lillian Werner, Jonathan Rosenberg, Sabina Signoretti, Marcella Callea, Toni K Choueiri, Gordon J Freeman, Joaquim Bellmunt
• Journal: Scientific reports (Sci Rep) Vol. 6 Pg. 27702 (06 10 2016) ISSN: 2045-2322 [Electronic] England
• PMID: 27283319 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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