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

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

Author information

1
Bladder Cancer Center, Dana-Farber Cancer Institute/Brigham and Women's Hospital, Boston MA, USA.
2
Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA, USA.
3
Memorial Sloan Kettering Cancer Center, New York, NY, USA.
4
Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA.
5
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
6
University Hospital del Mar-IMIM, Barcelona, Spain.

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.

PMID:
27283319
PMCID:
PMC4901342
DOI:
10.1038/srep27702
[Indexed for MEDLINE]
Free PMC Article

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