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Expression Analyses Point to Comparable Subtypes in Human, Canine Invasive Bladder Cancers

NEW YORK (GenomeWeb) – A Purdue University- and National Cancer Institute-led team has uncovered comparable gene expression profiles in tumors from human and canine forms of invasive urothelial carcinoma (iUC), suggesting dogs that develop the disease naturally may help in findings ways to effectively classify and treat it in humans.

As they reported online this week in PLOS One, the researchers did array-based gene expression profiling on tumor or normal bladder tissue from more than a dozen dogs. As in previously profiled samples from humans with iUC, they found that the canine iUC cases fell into expression-based luminal and basal subtypes similar to those found in breast cancer.

And as in past studies of invasive bladder cancer in humans, the canine iUC cases tended to be marked by enhanced expression of genes involved in the P53 and epidermal growth factor receptor signaling pathways, pointing to molecular overlap between human and canine iUC tumors.

"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 iUC," corresponding author Deborah Knapp, an oncology and veterinary clinical sciences researcher at Purdue University, and her colleagues wrote.

Invasive urothelial cancer is among the most fatal forms of bladder cancer, accounting for more than 160,000 global deaths per year, the researchers noted. Because dogs sometimes develop the disease spontaneously, they speculated that tracking iUC development, disease patterns, and treatment outcomes in canines could augment efforts to staunch canine and human forms of the disease.

The group isn't the first to search for clinical clues in spontaneous canine cancers. At the American Society for Clinical Oncology annual meeting earlier this year, a North Carolina State University researcher described efforts to characterize copy number patterns and other molecular features in dogs with bladder or other cancer types.

For the current study, Knapp and her colleagues used Affymetrix canine 2.0 arrays to profile gene expression patterns in tumor samples from 18 dogs with iUC and bladder samples from four healthy dogs.

They also tapped into expression data on eight human iUC tumor and seven normal samples in the Gene Expression Omnibus database that had been profiled using the Affymetrix Human Genome U133 Plus 2.0 array.

After narrowing in on genes represented on both the canine and human expression chips, the team looked at whether differentially expressed genes in tumor and normal bladder samples overlap with those showing distinct expression patterns in canine iUC tumors, compared to normal dog bladder tissue.

From the 436 comparable genes scrutinized in both human and dog samples, the researchers saw that the iUC tumors and normal bladder tissue samples generally clustered together across the two species.

Along with a cluster containing normal bladder samples, their results revealed expression-based subtypes within the tumor samples — particularly subtypes with transcript profiles resembling those in basal or luminal breast cancer subtypes.

Given these and other similarities between human and canine iUC cases, the study's authors argued that "[n]aturally occurring iUC in dogs offers several features that complement other animal models of bladder cancer."

"[M]any pet owners, as well as comparative oncology researchers, view clinical trials in dogs as a win-win-win scenario," they noted. "The individual dog gains access to a treatment that is expected to be beneficial and well tolerated, and pet owners embrace the possibility that their dog's participation will provide information that could help other dogs and humans facing cancer."