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Comparative Multi-Omics Evaluation of the Tumor Microenvironment in Canine and Human Hepatocellular Carcinoma

ABSTRACT: Background: Liver cancer remains a leading cause of death in humans. Its primary form, hepatocellular carcinoma (HCC) is frequently resistant to chemotherapy and radiation and often shows insufficient response to immunotherapy. HCC in dogs can arise from various factors but is not typically associated with viral infections, cirrhosis, or alcohol consumption, the more common triggers of spontaneous HCC in humans. This distinction offers a unique comparative perspective on the intrinsic genetic drivers of the disease. Methods: Using whole exome sequencing (WES) and single nucleus RNA sequencing (snRNA-seq) in tandem, we perform a multi-omic analysis of the dog HCC tumor. Results: Mutational analysis of impactful polymorphisms revealed a conserved cross-species landscape with genes such as CTNNB1, known for highly recurrent mutations in human HCC, showing similar alterations in dogs. In dog HCC tumors, we identified major cell types commonly observed in human HCC, including T lymphocyte, endothelial, macrophage, fibroblast, hepatocyte, malignant, and non-specific proliferating types. A comparative analysis of intercellular interactions across human and dog HCC cell types revealed intriguing parallels, particularly in macrophage functionality. Conclusions: These findings underscore the need for expanded genetic studies of dog HCC to further elucidate cross-species commonalities, offering deeper insights into key aspects of HCC biology and identifying novel therapeutic targets.

ORGANISM(S): Canis lupus familiaris

PROVIDER: GSE292303 | GEO | 2026/05/31

REPOSITORIES: GEO

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Project description:Dogs are commonly used models of human inherited retinal disorders. Because the dog retina contains a macula-like region, dogs are susceptible to maculopathies with many shared genetic etiologies with humans. Human macular gene expression has been characterized and provides insight into the underlying basis of macular disease. We sought to compare macular gene expression profiles in dogs and humans and interrogate macular disease-associated genes for differential expression between macula and periphery. RNA sequencing was performed on 8mm samples of the dog macular region and superior peripheral region, sampling retina and retinal pigmented epithelium/choroid separately. Read sequences were mapped to CanFam3.1 and raw read counts were analyzed to determine significantly differentially expressed genes between macula and periphery within each tissue. A similar analytic pipeline was used with a published dataset of human samples to allow direct dog/human comparisons. Pathways and processes involved in significantly DEGs were identified using the Database for Annotation, Visualization and Integrated Discovery. Dogs and humans shared the extent and direction of macular retinal differential gene expression, with multiple shared biological pathways implicated in differential expression. There were fewer similarities between dog and human in the supporting tissues of the retina (the RPE, choroid, sclera). Many genes implicated in heritable retinal and macular disorders in both dogs and humans were differentially expressed between macula and periphery. Approximately 2/3 of genes associated with human age-related macular degeneration were differentially expressed in at least one human tissue, whereas approximately half were differentially expressed in at least one dog tissue. This work underpins the dog macular retinal region as analogous to the human macula in terms of differential gene expression. Whilst age-related maculopathy has not been described in dogs, evidence supports the study of aging of the macula and susceptibility to age-associated pathology in dogs.

Project description:Shigui Ruan. Modeling the transmission dynamics and control of rabies in China. Mathematical Biosciences 286 (2017). Human rabies was first recorded in ancient China in about 556 BC and is still one of the major public-health problems in China. From 1950 to 2015, 130,494 human rabies cases were reported in Mainland China with an average of 1977 cases per year. It is estimated that 95% of these human rabies cases are due to dog bites. The purpose of this article is to provide a review about the models, results, and simulations that we have obtained recently on studying the transmission of rabies in China. We first construct a basic susceptible, exposed, infectious, and recovered (SEIR) type model for the spread of rabies virus among dogs and from dogs to humans and use the model to simulate the human rabies data in China from 1996 to 2010. Then we modify the basic model by including both domestic and stray dogs and apply the model to simulate the human rabies data from Guangdong Province, China. To study the seasonality of rabies, in Section 4 we further propose a SEIR model with periodic transmission rates and employ the model to simulate the monthly data of human rabies cases reported by the Chinese Ministry of Health from January 2004 to December 2010. To understand the spatial spread of rabies, in Section 5 we add diffusion to the dog population in the basic SEIR model to obtain a reaction-diffusion equation model and determine the minimum wave speed connecting the disease-free equilibrium to the endemic equilibrium. Finally, in order to investigate how the movement of dogs affects the geographically inter-provincial spread of rabies in Mainland China, in Section 6 we propose a multi-patch model to describe the transmission dynamics of rabies between dogs and humans and use the two-patch submodel to investigate the rabies virus clades lineages and to simulate the human rabies data from Guizhou and Guangxi, Hebei and Fujian, and Sichuan and Shaanxi, respectively. Some discussions are provided in Section 7.

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Comparative Multi-Omics Evaluation of the Tumor Microenvironment in Canine and Human Hepatocellular Carcinoma

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