Correlation of Apobec Mrna Expression with overall Survival and pd-l1 Expression in Urothelial Carcinoma.
Correlation of Apobec Mrna Expression with overall Survival and pd-l1 Expression in Urothelial Carcinoma.
复制标题
DOI：
10.1038/srep27702
复制
发表时间：
2016-06-10
影响因子：
4.6
通讯作者：
Bellmunt J
中科院分区：
文献类型：
--
作者：
Mullane SA;Werner L;Rosenberg J;Signoretti S;Callea M;Choueiri TK;Freeman GJ;Bellmunt J
转移性尿路上皮癌（mUC）具有非常高的突变率，并且与APOBEC突变标签相关。我们研究了73例mUC患者队列中APOBEC表达与总生存期（OS）和PD-L1表达的相关性。使用Nanostring测量APOBEC 3基因家族（A3 A、A3 B、A3 C、A3F_a、A3F_b、A3 G、A3 H）的mRNA表达。通过免疫组织化学评价的肿瘤浸润单核细胞（TIMCs）和肿瘤细胞上的PD-L1表达评分为0 - 4，2-4为阳性。Wilcoxon的非参数检验评估了APOBEC和PD-L1的相关性。考克斯回归模型评估APOBEC与OS的关联。所有APOBEC基因在mUC中表达。A3 A、A3 D和A3 H表达增加与PD-L1阳性TIMCs相关（p = 0.0009、0.009、0.06）。A3 B表达降低与PD-L1阳性TIMCs表达轻微相关（p = 0.05）。A3F_a和A3F_b表达增加与肿瘤细胞上PD-L1表达增加相关（p = 0.05）。A3 D和A3 H表达增加与OS延长相关（p = 0.0009）。特定的APOBEC基因在生存和PD-L1表达方面对mUC有不同的影响。A3 D和A3 H可能在mUC中具有最重要的作用，因为它们与OS和PD-L1 TIMC表达相关。
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.