scholarly journals A Comparative Meta-Analysis and in silico Analysis of Differentially Expressed Genes and Proteins in Canine and Human Bladder Cancer

2020 ◽  
Vol 7 ◽  
Author(s):  
Victoria Vitti Gambim ◽  
Renee Laufer-Amorim ◽  
Ricardo Henrique Fonseca Alves ◽  
Valeria Grieco ◽  
Carlos Eduardo Fonseca-Alves
2020 ◽  
Author(s):  
Victoria Vitti Gambim ◽  
Renee Laufer-Amorim ◽  
Ricardo Fonseca Alves ◽  
Valeria Grieco ◽  
Carlos Eduardo Fonseca-Alves

AbstractCanine and human bladder cancer present several similar anatomical, morphological and molecular characteristics and dogs can be considered a model for human bladder cancer. However, the veterinary literature lacks information regarding cross validation analysis between human and canine large-scale data. Therefore, this research aimed to perform a meta-analysis of the previous canine literature on bladder cancer, identifying genes and protein previously evaluated in these studies. Besides that, we also performed a cross validation of the canine transcriptome data and the human data from The Cancer Genome Atlas (TCGA) to identify potential markers for both species. It was performed a meta-analysis using the following indexing terms “bladder” AND “carcinoma” AND “dog” in different international databases and 385 manuscripts were identified in our initial search. Then, several inclusion criteria were applied and only 25 studies met these criteria. Among these studies, five presented transcriptome data and 20 evaluated only isolated genes or proteins.Regarding the studies involving isolated protein analysis, HER-2 protein was the most studied (3/20), followed by TAG-72 (2/20), COX-2 (2/2), Survivin (2/2) and CK7 (2/2). Regarding the cross-validation analysis of human and canine transcriptome data, we identified 35 deregulated genes, including ERBB2, TP53, EGFR and E2F2. Our results demonstrated that the previous canine literature on bladder cancer was focused on the evaluation of isolated markers with no association with patient’s survival. Besides that, the lack of information regarding tumor muscle-invasion can be considered an important limitation when comparing human and canine bladder tumors. Our in-silico analysis involving canine and human transcriptome data provided several genes with potential to be markers for both human and canine bladder tumors and these genes should be considered for future studies on canine bladder cancer.


2019 ◽  
Vol 20 (5) ◽  
pp. 1017 ◽  
Author(s):  
Jen-Jie Lin ◽  
Chun-Chieh Huang ◽  
Yu-Li Su ◽  
Hao-Lun Luo ◽  
Nai-Lun Lee ◽  
...  

Tangeretin is one of the most abundant compounds in citrus peel, and studies have shown that it possesses anti-oxidant and anti-cancer properties. However, no study has been conducted on bladder cancer cells. Bladder cancer has the second highest mortality rate among urological cancers and is the fifth most common malignancy in the world. Currently, combination chemotherapy is the most common approach by which to treat patients with bladder cancer, and thus identifying more effective chemotherapeutic agents that can be safely administered to patients is a very important research issue. Therefore, this study investigated whether tangeretin can induce apoptosis and identified the signaling pathways of tangeretin-induced apoptosis in human bladder cancer cells using two-dimensional gel electrophoresis (2DGE). The results of the study demonstrated that 60 μM tangeretin reduced the cell survival of a BFTC-905 bladder carcinoma cell line by 42%, and induced early and late apoptosis in the cells. In this study 2DGE proteomics technology identified 41 proteins that were differentially-expressed in tangeretin-treated cells, and subsequently LC–MS/MS analysis was performed to identify the proteins. Based on the functions of the differentially-expressed proteins, the results suggested that tangeretin caused mitochondrial dysfunction and further induced apoptosis in bladder cancer cells. Moreover, western blotting analysis demonstrated that tangeretin treatment disturbed calcium homeostasis in the mitochondria, triggered cytochrome C release, and activated caspase-3 and caspase-9, which led to apoptosis. In conclusion, our results showed that tangeretin-induced apoptosis in human bladder cancer cells is mediated by mitochondrial inactivation, suggesting that tangeretin has the potential to be developed as a new drug for the treatment of bladder cancer.


PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0248342
Author(s):  
Daniel Uysal ◽  
Karl-Friedrich Kowalewski ◽  
Maximilian Christian Kriegmair ◽  
Ralph Wirtz ◽  
Zoran V. Popovic ◽  
...  

Technological advances in molecular profiling have enabled the comprehensive identification of common regions of gene amplification on chromosomes (amplicons) in muscle invasive bladder cancer (MIBC). One such region is 8q22.2, which is largely unexplored in MIBC and could harbor genes with potential for outcome prediction or targeted therapy. To investigate the prognostic role of 8q22.2 and to compare different amplicon definitions, an in-silico analysis of 357 patients from The Cancer Genome Atlas, who underwent radical cystectomy for MIBC, was performed. Amplicons were generated using the GISTIC2.0 algorithm for copy number alterations (DNA_Amplicon) and z-score normalization for mRNA gene overexpression (RNA_Amplicon). Kaplan-Meier survival analysis, univariable, and multivariable Cox proportional hazard ratios were used to relate amplicons, genes, and clinical parameters to overall (OS) and disease-free survival (DFS). Analyses of the biological functions of 8q22.2 genes and genomic events in MIBC were performed to identify potential targets. Genes with prognostic significance from the in silico analysis were validated using RT-qPCR of MIBC tumor samples (n = 46). High 8q22.2 mRNA expression (RNA-AMP) was associated with lymph node metastases. Furthermore, 8q22.2 DNA and RNA amplified patients were more likely to show a luminal subtype (DNA_Amplicon_core: p = 0.029; RNA_Amplicon_core: p = 0.01). Overexpression of the 8q22.2 gene OSR2 predicted shortened DFS in univariable (HR [CI] 1.97 [1.2; 3.22]; p = 0.01) and multivariable in silico analysis (HR [CI] 1.91 [1.15; 3.16]; p = 0.01) and decreased OS (HR [CI] 6.25 [1.37; 28.38]; p = 0.0177) in RT-qPCR data analysis. Alterations in different levels of the 8q22.2 region are associated with manifestation of different clinical characteristics in MIBC. An in-depth comprehensive molecular characterization of genomic regions involved in cancer should include multiple genetic levels, such as DNA copy number alterations and mRNA gene expression, and could lead to a better molecular understanding. In this study, OSR2 is identified as a potential biomarker for survival prognosis.


2021 ◽  
Vol 62 (4) ◽  
pp. 316-324
Author(s):  
Susan Omar Rasool ◽  
Ata Mirzaei Nahr ◽  
Sania Eskandari ◽  
Milad Hosseinzadeh ◽  
Soheila Asoudeh Moghanloo ◽  
...  

While COVID-19 liver injuries have been reported in various studies, concerns are raised about disease-drug reactions in COVID-19 patients. In this study, we examined the hypothesis of gene-disease interactions in an in-silico model of gene expression to seek changes in cytochrome P450 genes. The Gene Expression Omnibus dataset of the liver autopsy in deceased COVID-19 patients (GSE150316) was used in this study. Non-alcoholic fatty liver biopsies were used as the control (GSE167523). Besides, gene expression analysis was performed using the DESeq/EdgeR method. The GO databases were used, and the paths were set at p<0.05. The drug-gene interaction database (DGIdb) was searched for interactions. According to the results, 5,147 genes were downregulated, and 5,122 genes were upregulated in SARS-CoV-2 compared to healthy livers. Compared to the cytochromes, 34 cytochromes were downregulated, while 4 cytochromes were upregulated among the detected differentially expressed genes (DEG). The drug-gene interaction database (DGIdb) provided a list of medications with potential interactions with COVID-19 as well as metacetamol, phenethyl isocyanate, amodiaquine, spironolactone, amiloride, acenocoumarol, clopidogrel, phenprocoumon, trimipramine, phenazepam, etc. Besides, dietary compounds of isoflavones, valerian, and coumarin, as well as caffeine metabolism were shown to have possible interactions with COVID-19 disease. Our study showed that expression levels of cytochrome P450 genes could get altered following COVID-19. In addition, a drug-disease interaction list is recommended to be used for evaluations in clinical considerations in further studies.


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