Correlation of Apobec Mrna Expression with overall survival and pd-l1 expression in urothelial carcinoma

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  • dc.contributor.author Mullane, Stephanie A.ca
  • dc.contributor.author Werner, Lillianca
  • dc.contributor.author Rosenberg, Jonathan E.ca
  • dc.contributor.author Signoretti, Sabinaca
  • dc.contributor.author Callea, Marcellaca
  • dc.contributor.author Choueiri, Toni K.ca
  • dc.contributor.author Freeman, Gordon J.ca
  • dc.contributor.author Bellmunt Molins, Joaquim, 1959-ca
  • dc.date.accessioned 2016-12-07T09:15:46Z
  • dc.date.issued 2016
  • dc.description.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.ca
  • dc.description.sponsorship This work has been supported by FIS PI10/02112 (microRNAS) (Spanish Health Ministry Grant “Fondo de Investigacion Sanitaria”) and RTICC 06/0020/19 grants. Fundació Cellex (Barcelona) provided a generous donation to the Group of Molecular Therapeutics and Biomarkers, Hospital del Mar. The Tumor Bank of the Department of Pathology of Hospital del Mar (RD09/0076/0036) and the Xarxa de Bancs de Tumors sponsored by Pla Director d’Oncologia de Catalunya (XBTC) provided tissue samples. This study was also possible thanks to a grant from Friends of Dana-Farber, the Retired Professional Fire Fighters Cancer Fund, and the generous support of Whole Foods Golf Classic for bladder cancer research in memoriam of Christopher Snell. Also a private donation in the memory of Rich Beaudoin. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscrip
  • dc.format.mimetype application/pdfca
  • dc.identifier.citation Mullane SA, Werner L, Rosenberg J, Signoretti S, Callea M, Choueiri TK. et al. 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/srep27702ca
  • dc.identifier.doi http://dx.doi.org/10.1038/srep27702
  • dc.identifier.issn 2045-2322
  • dc.identifier.uri http://hdl.handle.net/10230/27698
  • dc.language.iso engca
  • dc.publisher Nature Publishing Groupca
  • dc.relation.ispartof Scientific Reports. 2016 Jun 10;6:27702
  • dc.rights This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ca
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by/4.0/
  • dc.subject.other Tumorsca
  • dc.subject.other Càncer -- Aspectes genèticsca
  • dc.title Correlation of Apobec Mrna Expression with overall survival and pd-l1 expression in urothelial carcinomaca
  • dc.type info:eu-repo/semantics/articleca
  • dc.type.version info:eu-repo/semantics/publishedVersionca

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