Correlation of Apobec Mrna Expression with overall Survival and pd-l1 Expression in Urothelial Carcinoma
Mullane, Stephanie A.
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CitationMullane, Stephanie A., Lillian Werner, Jonathan Rosenberg, Sabina Signoretti, Marcella Callea, Toni K. Choueiri, Gordon J. Freeman, and Joaquim Bellmunt. 2016. “Correlation of Apobec Mrna Expression with overall Survival and pd-l1 Expression in Urothelial Carcinoma.” Scientific Reports 6 (1): 27702. doi:10.1038/srep27702. http://dx.doi.org/10.1038/srep27702.
AbstractMetastatic 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.
Citable link to this pagehttp://nrs.harvard.edu/urn-3:HUL.InstRepos:27662055
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