Project description:BackgroundFeline mammary carcinoma (FMC) is a common aggressive and highly metastatic cancer affecting female cats. Early detection is essential for preventing local and distant metastasis, thereby improving overall survival rates. While acquiring molecular data before surgery offers significant potential benefits, the current protein biomarkers for monitoring disease progression in non-metastatic FMC (NmFMC) and metastatic FMC (mFMC) are limited. The objective of this study was to investigate the serum peptidome profiles of NmFMC and mFMC using liquid chromatography-tandem mass spectrometry. A cross-sectional study was conducted to compare serum peptidome profiles in 13 NmFMC, 23 mFMC and 18 healthy cats. The liquid chromatography-tandem mass spectrometry analysis was performed on non-trypsinized samples.ResultsOut of a total of 8284 expressed proteins observed, several proteins were found to be associated with human breast cancer. In NmFMC, distinctive protein expressions encompassed double-stranded RNA-binding protein Staufen homolog 2 (STAU2), associated with cell proliferation, along with bromodomain adjacent to zinc finger domain 2A (BAZ2A) and gamma-aminobutyric acid type A receptor subunit epsilon (GABRE), identified as potential treatment targets. Paradoxically, positive prognostic markers emerged, such as complement C1q like 3 (C1QL3) and erythrocyte membrane protein band 4.1 (EPB41 or 4.1R). Within the mFMC group, overexpressed proteins associated with poor prognosis were exhibited, including B-cell lymphoma 6 transcription repressor (BCL6), thioredoxin reductase 3 (TXNRD3) and ceruloplasmin (CP). Meanwhile, the presence of POU class 5 homeobox (POU5F1 or OCT4) and laminin subunit alpha 1 (LAMA1), reported as metastatic biomarkers, was noted.ConclusionThe presence of both pro- and anti-proliferative proteins was observed, potentially indicating a distinctive characteristic of NmFMC. Conversely, proteins associated with poor prognosis and metastasis were noted in the mFMC group.

Project description:[original title] Metastatic Canine Mammary Carcinomas can be Identified by a Gene Expression Profile that partly Overlaps with Human Breast Cancer Profiles. Introduction: Similar to human breast cancer mammary tumors of the female dog are commonly associated with a fatal outcome due to the development of distant metastases. However, the molecular defects leading to metastasis are largely unknown and the value of canine mammary carcinoma as a model for human breast cancer is unclear. In this study, we analyzed the gene expression signatures associated with mammary tumor metastasis and asked for parallels with the human equivalent. Methods: Messenger RNA expression profiles of twenty-seven lymph node metastasis positive or negative canine mammary carcinomas were established by microarray analysis. Differentially expressed genes were functionally characterized and associated with molecular pathways. The findings were also correlated with published data on human breast cancer. Results: Metastatic canine mammary carcinomas had 1,011 significantly differentially expressed genes when compared to non-metastatic carcinomas. Metastatic carcinomas had a significant up-regulation of genes associated with cell cycle regulation, matrix modulation, protein folding and proteasomal degradation whereas cell differentiation genes, growth factor pathway genes and regulators of actin organization were significantly down-regulated. Interestingly, 265 of the 1,011 differentially expressed canine genes are also related to human breast cancer and, vice versa, parts of a human prognostic gene signature were identified in the expression profiles of the metastatic canine tumors. Conclusions: Metastatic canine mammary carcinomas can be discriminated from non-metastatic carcinomas by their gene expression profiles. More than one third of the differentially expressed genes are also described of relevance for human breast cancer. Many of the differentially expressed genes are linked to functions and pathways which appear to be relevant for the induction and maintenance of metastatic progression and may represent new therapeutic targets. Furthermore, dogs are in some aspects suitable as a translational model for human breast tumors in order to identify prognostic molecular signatures and potential therapeutic targets. Thirteen simple mammary carcinomas with invasive growth and lymph node metastases at the time of tumor resection and 14 simple carcinomas without lymph node metastases were included in the study. None of the patients had radiographically detectable pulmonary metastases at the time of tumor resection. Distant metastases as the cause of death were determined postoperatively by radiographic detection of metastases or necropsy. Selection criteria for carcinomas without lymph node metastases included an invasive growth, a negative lymph node status, a histological grade III and a minimal tumor diameter above the average of the lymph node positive tumors (> 2.42 cm). All animals with non-metastatic carcinomas had a survival rate of over 24 months except animal no. 22 (2627) which developed radiographic detectable lung metastases 8 months after surgery. Tumor and lymph node histologies were evaluated independently by two board-certified pathologists, following the criteria of the WHO classification of canine mammary tumors and the Nottingham grading system. All 27 tumors were simple carcinomas and characterized by an invasive, mostly solid growth pattern, marked cellular pleomorphism, anisokaryosis and 3 or more mitotic figures per high power field.

Project description:[original title] Metastatic Canine Mammary Carcinomas can be Identified by a Gene Expression Profile that partly Overlaps with Human Breast Cancer Profiles. Introduction: Similar to human breast cancer mammary tumors of the female dog are commonly associated with a fatal outcome due to the development of distant metastases. However, the molecular defects leading to metastasis are largely unknown and the value of canine mammary carcinoma as a model for human breast cancer is unclear. In this study, we analyzed the gene expression signatures associated with mammary tumor metastasis and asked for parallels with the human equivalent. Methods: Messenger RNA expression profiles of twenty-seven lymph node metastasis positive or negative canine mammary carcinomas were established by microarray analysis. Differentially expressed genes were functionally characterized and associated with molecular pathways. The findings were also correlated with published data on human breast cancer. Results: Metastatic canine mammary carcinomas had 1,011 significantly differentially expressed genes when compared to non-metastatic carcinomas. Metastatic carcinomas had a significant up-regulation of genes associated with cell cycle regulation, matrix modulation, protein folding and proteasomal degradation whereas cell differentiation genes, growth factor pathway genes and regulators of actin organization were significantly down-regulated. Interestingly, 265 of the 1,011 differentially expressed canine genes are also related to human breast cancer and, vice versa, parts of a human prognostic gene signature were identified in the expression profiles of the metastatic canine tumors. Conclusions: Metastatic canine mammary carcinomas can be discriminated from non-metastatic carcinomas by their gene expression profiles. More than one third of the differentially expressed genes are also described of relevance for human breast cancer. Many of the differentially expressed genes are linked to functions and pathways which appear to be relevant for the induction and maintenance of metastatic progression and may represent new therapeutic targets. Furthermore, dogs are in some aspects suitable as a translational model for human breast tumors in order to identify prognostic molecular signatures and potential therapeutic targets.

Project description:Purpose: Photoperiod is known to cause physiological changes in seasonal mammals, including body weight, physical activity, and reproductive status. Because cats are seasonal breeders, we recently tested the effects of day length on resting metabolic rate, voluntary physical activity, and food intake. In that study, resting metabolic rate, physical activity, and food intake to maintain body weight were greater in cats exposed to long days vs. short days. Because photoperiod has also been demonstrated to affect adipose tissue gene expression in several species, including dairy cows, sheep, and Siberian hamsters, the objective of this study was to determine the effects of day length on the adipose transcriptome profile of cats as assessed by RNA-seq. Methods: Ten healthy adult neutered male domestic shorthair cats were used in a randomized crossover design study. During two 12-wk periods, cats were exposed to either short days (8 hr light:16 hr dark) or long days (16 hr light:8 hr dark). Cats were fed a commercial diet to maintain baseline body weight. Subcutaneous adipose biopsies were collected at wk 12 of each period for RNA isolation and Illumina sequencing. Results: A total of 578 million sequences (28.9 million/sample) were generated by Illumina sequencing. Using a raw p value of P<0.005, 170 mRNA transcripts were differentially expressed between short day- and long day-housed cats. Of the 170 transcripts highlighted, 25 annotated transcripts were up-regulated, while 116 annotated transcripts were down-regulated by long days. Another 29 un-annotated transcripts (name and function not known) were also different between groups. In general, adipose tissue of long day-housed cats had greater expression of genes involved with cholesterol trafficking, fatty acid synthesis and immune function, and lower expression of genes involved with cell cycle and growth, cell development and structure, and protein processing, when compared to short day-housed cats. Subcutaneous adipose tissue mRNA profiles of healthy adult neutered male cats exposed to short days (8 hr light: 16 hr dark) or long days (16 hr light: 8 hr dark) using Illumina sequencing.

Project description:Purpose: Photoperiod is known to cause physiological changes in seasonal mammals, including body weight, physical activity, and reproductive status. Because cats are seasonal breeders, we recently tested the effects of day length on resting metabolic rate, voluntary physical activity, and food intake. In that study, resting metabolic rate, physical activity, and food intake to maintain body weight were greater in cats exposed to long days vs. short days. Because photoperiod has also been demonstrated to affect adipose tissue gene expression in several species, including dairy cows, sheep, and Siberian hamsters, the objective of this study was to determine the effects of day length on the adipose transcriptome profile of cats as assessed by RNA-seq. Methods: Ten healthy adult neutered male domestic shorthair cats were used in a randomized crossover design study. During two 12-wk periods, cats were exposed to either short days (8 hr light:16 hr dark) or long days (16 hr light:8 hr dark). Cats were fed a commercial diet to maintain baseline body weight. Subcutaneous adipose biopsies were collected at wk 12 of each period for RNA isolation and Illumina sequencing. Results: A total of 578 million sequences (28.9 million/sample) were generated by Illumina sequencing. Using a raw p value of P<0.005, 170 mRNA transcripts were differentially expressed between short day- and long day-housed cats. Of the 170 transcripts highlighted, 25 annotated transcripts were up-regulated, while 116 annotated transcripts were down-regulated by long days. Another 29 un-annotated transcripts (name and function not known) were also different between groups. In general, adipose tissue of long day-housed cats had greater expression of genes involved with cholesterol trafficking, fatty acid synthesis and immune function, and lower expression of genes involved with cell cycle and growth, cell development and structure, and protein processing, when compared to short day-housed cats.

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Serum peptidome profiles in metastatic and non-metastatic feline mammary carcinoma

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