Neoplastic signatures: Comparative proteomics of canine hepatobiliary neuroendocrine tumors to normal niche tissue

Abstract

Hepatobiliary neuroendocrine neoplasms are rare cancers in humans and dogs. To date, no large-scale primary hepatobiliary neoplasm omics analyses exist in any species. This limits the development of diagnostic biomarkers and targeted therapeutics. Neuroendocrine cancers are a heterogenous group of neoplasms categorized by their tissue-of-origin. Because the anatomic niche of neuroendocrine neoplasms shapes tumor phenotype, we sought to compare the proteomes of 3 canine hepatobiliary neoplasms to normal hepatobiliary tissue and adrenal glands with the objective of identifying unique protein signatures. Protein was extracted from formalin-fixed paraffin-embedded samples and submitted for tandem mass spectroscopy. Thirty-two upregulated and 126 downregulated differentially expressed proteins were identified. Remarkably, 6 (19%) of the upregulated proteins are correlated to non-hepatobiliary neuroendocrine neoplasia and 16 (50%) are functionally annotated within the exosome cellular compartment key to neuroendocrine signaling. Twenty-six (21%) downregulated proteins are enriched in metabolic pathways consistent with alterations in cancer. These results suggests that characteristic neoplastic protein signatures can be gleaned from small data sets using a comparative proteomics approach.

Omics Technologies in Veterinary Medicine: Literature Review and Perspectives in Transfusion Medicine

“…Given these premises for human medicine, and given that omics technologies are currently expensive and hardly accessible to researchers, it is consequently unavoidable that a great deal of progress is still needed, especially in veterinary medicine. In the veterinary literature, the omics approach has been investigated by a few studies focusing on fields such as oncology [87], nutrition [132], endocrinology [94], cardiology [90], and nephrology [98]. Then other pioneering studies [30, 125] have proposed omics datasets that, although in need of validation, pave the way for future comparative research among human and nonhuman species.…”

“…Major attention has been paid to veterinary oncology, not least because of the comparative insights with humans it provides. In particular, neoplastic diseases investigated through omics technologies are hematopoietic neoplasms [79][80][81][82], mammary tumors [83][84][85], oral neoplasms [86], neuroendocrine tumors [87], and melanocytic tumors [73,88]. Further disorders addressed by omics approaches include cardiopathies [89][90][91], endocrinopathies such as hyperadrenocorticism [92] and diabetes mellitus [93,94], hepatopathies [95][96][97], chronic kidney disease [98,99], and inflammatory/infectious diseases(i.e., sepsis [100], pyometra [101], and vector-borne diseases [102,103]).…”