Immune checkpoint B7x (B7-H4/B7S1/VTCN1) is over expressed in spontaneous canine bladder cancer

the first report and its implications in a preclinical model

Damini Chand, Deepika Dhawan, Alexander I. Sankin, Xiaoxin Ren, Juan Lin, Mark P. Schoenberg, Deborah W. Knapp, Xingxing Zang

Research output: Contribution to journalArticle

Abstract

Background: 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. Objective: This work aims to study expression of immune checkpoint B7x in spontaneous canine invasive bladder cancer. Methods: 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). Results:RNA-seq analysis indicated 5.72 and 7.04 fold up regulation of B7x in tumors, using DESeq2 and edgeRrespectively (p < 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% (n = 20/50), low in 24% (n = 12/50), medium in 14% (n = 7/50) and high in 22% (n = 11/50) of cases. In human BLCA, B7x expression was significantly associated with worse overall survival (p = 0.02). Conclusions: 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.

Original languageEnglish (US)
Pages (from-to)63-71
Number of pages9
JournalBladder Cancer
Volume5
Issue number1
DOIs
StatePublished - Jan 1 2019

Fingerprint

Urinary Bladder Neoplasms
Canidae
Gene Ontology
Urinary Bladder
Carcinoma
Immunohistochemistry
RNA
Neoplasms
Translational Medical Research
Immunosuppressive Agents
Up-Regulation
Survival
Therapeutics
Proteins

Keywords

  • Canine bladder cancer
  • Human bladder urothelial carcinoma
  • Immune checkpoint
  • Immunotherapy

ASJC Scopus subject areas

  • Oncology
  • Urology

Cite this

Immune checkpoint B7x (B7-H4/B7S1/VTCN1) is over expressed in spontaneous canine bladder cancer : the first report and its implications in a preclinical model. / Chand, Damini; Dhawan, Deepika; Sankin, Alexander I.; Ren, Xiaoxin; Lin, Juan; Schoenberg, Mark P.; Knapp, Deborah W.; Zang, Xingxing.

In: Bladder Cancer, Vol. 5, No. 1, 01.01.2019, p. 63-71.

Research output: Contribution to journalArticle

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abstract = "Background: 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. Objective: This work aims to study expression of immune checkpoint B7x in spontaneous canine invasive bladder cancer. Methods: 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). Results:RNA-seq analysis indicated 5.72 and 7.04 fold up regulation of B7x in tumors, using DESeq2 and edgeRrespectively (p < 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{\%} (n = 20/50), low in 24{\%} (n = 12/50), medium in 14{\%} (n = 7/50) and high in 22{\%} (n = 11/50) of cases. In human BLCA, B7x expression was significantly associated with worse overall survival (p = 0.02). Conclusions: 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.",
keywords = "Canine bladder cancer, Human bladder urothelial carcinoma, Immune checkpoint, Immunotherapy",
author = "Damini Chand and Deepika Dhawan and Sankin, {Alexander I.} and Xiaoxin Ren and Juan Lin and Schoenberg, {Mark P.} and Knapp, {Deborah W.} and Xingxing Zang",
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T2 - the first report and its implications in a preclinical model

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AU - Dhawan, Deepika

AU - Sankin, Alexander I.

AU - Ren, Xiaoxin

AU - Lin, Juan

AU - Schoenberg, Mark P.

AU - Knapp, Deborah W.

AU - Zang, Xingxing

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AB - Background: 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. Objective: This work aims to study expression of immune checkpoint B7x in spontaneous canine invasive bladder cancer. Methods: 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). Results:RNA-seq analysis indicated 5.72 and 7.04 fold up regulation of B7x in tumors, using DESeq2 and edgeRrespectively (p < 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% (n = 20/50), low in 24% (n = 12/50), medium in 14% (n = 7/50) and high in 22% (n = 11/50) of cases. In human BLCA, B7x expression was significantly associated with worse overall survival (p = 0.02). Conclusions: 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.

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