Chand Damini, Dhawan Deepika, Sankin Alexander, Ren Xiaoxin, Lin Juan, Schoenberg Mark, Knapp Deborah W, Zang Xingxing
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, USA.
Department of Urology, Montefiore Medical Center and Albert Einstein College of Medicine, Bronx, NY, USA.
Bladder Cancer. 2019 Jan 31;5(1):63-71. doi: 10.3233/BLC-180204.
B7x (B7-H4/B7S1/VTCN1), an inhibitory immune checkpoint molecule is a potential therapeutic target owing to its immunosuppressive effect and well-known expression in cancers. Immune checkpoints in canine bladder cancer are largely undefined. Here, we report the first evaluation on expression of B7x in spontaneous canine invasive bladder cancer, a novel model system for the study of invasive human urothelial carcinoma.
This work aims to study expression of immune checkpoint B7x in spontaneous canine invasive bladder cancer.
RNA-seq analysis was performed to determine B7x expression in tumor versus normal bladder. Gene ontology (GO) study was used to explore the biological role of B7x. B7x protein expression was evaluated by immunohistochemistry (IHC). TCGA and GTEx were used to examine B7x expression in 599 human bladder urothelial carcinoma (BLCA).
RNA-seq analysis indicated 5.72 and 7.04 fold up regulation of B7x in tumors, using DESeq2 and edge R respectively ( < 0.00008). B7x was closely associated with immune processes in GO analysis. IHC results revealed 60% of cases as B7x positive. B7x intensity was scored as negative in 40% ( = 20/50), low in 24% ( = 12/50), medium in 14% ( = 7/50) and high in 22% ( = 11/50) of cases. In human BLCA, B7x expression was significantly associated with worse overall survival ( = 0.02).
Our results suggest that B7x is over expressed in canine bladder cancer. Thus canine model can be vital in advancing the translational research on B7x, a new potential therapeutic target in human bladder cancer.
B7x（B7-H4/B7S1/VTCN1）是一种抑制性免疫检查点分子，因其免疫抑制作用以及在癌症中众所周知的表达情况，是一个潜在的治疗靶点。犬膀胱癌中的免疫检查点在很大程度上尚不明确。在此，我们报告了对自发性犬浸润性膀胱癌中B7x表达的首次评估，这是一种用于研究浸润性人类尿路上皮癌的新型模型系统。
本研究旨在探讨免疫检查点B7x在自发性犬浸润性膀胱癌中的表达情况。
进行RNA测序分析以确定肿瘤与正常膀胱中B7x的表达。采用基因本体（GO）研究来探索B7x的生物学作用。通过免疫组织化学（IHC）评估B7x蛋白表达。利用癌症基因组图谱（TCGA）和基因型组织表达（GTEx）数据库检测599例人类膀胱尿路上皮癌（BLCA）中B7x的表达。
RNA测序分析表明，使用DESeq2和edgeR软件分别检测到肿瘤中B7x上调了5.72倍和7.04倍（<0.00008）。GO分析显示B7x与免疫过程密切相关。免疫组化结果显示60%的病例为B7x阳性。在40%（20/50）的病例中B7x强度评分为阴性，24%（12/50）为低表达，14%（7/50）为中等表达，22%（11/50）为高表达。在人类BLCA中，B7x表达与较差的总生存期显著相关（P = 0.02）。
我们的结果表明B7x在犬膀胱癌中过度表达。因此，犬模型对于推进B7x的转化研究至关重要，B7x是人类膀胱癌中一个新的潜在治疗靶点。
