Correlation of Apobec Mrna Expression with overall Survival and pd-l1 Expression in Urothelial Carcinoma.
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.
Bladder Cancer Center, Dana-Farber Cancer Institute/Brigham and Women's Hospital, Boston MA, USA.
Stephanie A
SA
Mullane
Bladder Cancer Center, Dana-Farber Cancer Institute/Brigham and Women's Hospital, Boston MA, USA.|Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA, USA.
Lillian
L
Werner
Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Jonathan
J
Rosenberg
Bladder Cancer Center, Dana-Farber Cancer Institute/Brigham and Women's Hospital, Boston MA, USA.|Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA.
Sabina
S
Signoretti
Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA.
Marcella
M
Callea
Bladder Cancer Center, Dana-Farber Cancer Institute/Brigham and Women's Hospital, Boston MA, USA.|Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Toni K
TK
Choueiri
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Gordon J
GJ
Freeman
Bladder Cancer Center, Dana-Farber Cancer Institute/Brigham and Women's Hospital, Boston MA, USA.|Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.|University Hospital del Mar-IMIM, Barcelona, Spain.
Joaquim
J
Bellmunt
D000071478:APOBEC Deaminases; D060890:B7-H1 Antigen / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D003564:Cytidine Deaminase; D043525:Cytosine Deaminase / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016019:Survival Analysis; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000473:pathology; D019459:Urothelium / Q000378:metabolism / Q000473:pathology*
D060890:B7-H1 Antigen; C423236:CD274 protein, human; D012333:RNA, Messenger; D043525:Cytosine Deaminase; D000071478:APOBEC Deaminases; C502889:APOBEC3 proteins, human; D003564:Cytidine Deaminase