Comparative Gene Expression Analyses Identify Luminal and Basal Subtypes of Canine Invasive Urothelial Carcinoma That Mimic Patterns in Human Invasive Bladder Cancer.
More than 160,000 people are expected to die from invasive urothelial carcinoma (iUC) this year worldwide. Research in relevant animal models is essential to improving iUC management. Naturally-occurring canine iUC closely resembles human iUC in histopathology, metastatic behavior, and treatment response, and could provide a relevant model for human iUC. The molecular characterization of canine iUC, however, has been limited. Work was conducted to compare gene expression array results between tissue samples from iUC and normal bladder in dogs, with comparison to similar expression array data from human iUC and normal bladder in the literature. Considerable similarities between enrichment patterns of genes in canine and human iUC were observed. These included patterns mirroring basal and luminal subtypes initially observed in human breast cancer and more recently noted in human iUC. Canine iUC samples also exhibited enrichment for genes involved in P53 pathways, as has been reported in human iUC. This is particularly relevant as drugs targeting these genes/pathways in other cancers could be repurposed to treat iUC, with dogs providing a model to optimize therapy. As part of the validation of the results and proof of principal for evaluating individualized targeted therapy, the overexpression of EGFR in canine bladder iUC was confirmed. The similarities in gene expression patterns between dogs and humans add considerably to the value of naturally-occurring canine iUC as a relevant and much needed animal model for human iUC. Furthermore, the finding of expression patterns that cross different pathologically-defined cancers could allow studies of dogs with iUC to help optimize cancer management across multiple cancer types. The work is also expected to lead to a better understanding of the biological importance of the gene expression patterns, and the potential application of the cross-species comparisons approach to other cancer types as well.
Department of Veterinary Clinical Sciences, Purdue University College of Veterinary Medicine, Purdue University, West Lafayette, Indiana, United States of America; Purdue Oncological Sciences Center, Purdue University, West Lafayette, Indiana, United States of America.
Deepika
D
Dhawan
CCR Comparative Oncology Program, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, United States of America.
Melissa
M
Paoloni
Department of Bioinformatics, Strand Genomics Inc, San Francisco, California, United States of America.
Shweta
S
Shukradas
Department of Bioinformatics, Strand Genomics Inc, San Francisco, California, United States of America.
Dipanwita Roy
DR
Choudhury
Department of Statistics, Purdue University, West Lafayette, Indiana, United States of America.
Bruce A
BA
Craig
Purdue Oncological Sciences Center, Purdue University, West Lafayette, Indiana, United States of America; Department of Comparative Pathobiology, Purdue University College of Veterinary Medicine, Purdue University, West Lafayette, Indiana, United States of America.
José A
JA
Ramos-Vara
Department of Oncology and Urology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
Noah
N
Hahn
Department of Veterinary Clinical Sciences, Purdue University College of Veterinary Medicine, Purdue University, West Lafayette, Indiana, United States of America.
Patty L
PL
Bonney
CCR Comparative Oncology Program, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, United States of America.
Chand
C
Khanna
Department of Veterinary Clinical Sciences, Purdue University College of Veterinary Medicine, Purdue University, West Lafayette, Indiana, United States of America; Purdue Oncological Sciences Center, Purdue University, West Lafayette, Indiana, United States of America; Purdue University Center for Cancer Research, Purdue University, West Lafayette, Indiana, United States of America.
Deborah W
DW
Knapp
D000818:Animals; D002295:Carcinoma, Transitional Cell / Q000235:genetics* / Q000473:pathology; D004195:Disease Models, Animal; D004285:Dogs; D005260:Female; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000473:pathology; D019459:Urothelium / Q000473:pathology*