Altered Caspase-8 Expression Cancer Compound perturbations Gene perturbations Tumor development Cancer metastasis Cancer treatments With a single gene, if you want to know whether this gene is associated with any diseases, what is the function of this gene or whether this gene is a potential drug target in pharmaceutical research. you can do literature search such as in pubmed, however, it will be time consuming and sometimes, it will give incomplete information. Our institute has subscription to a commercial alternative nextbio.

Nextbio Nextbio is a life science search engine and it provides an unified interface for researchers to easily formulate and test new hypotheses across vast collections of experimental data. Nextbio collected public data from GEO, Array Express, SMD, etc and then use their analysis pipeline to process the data before manual tagging resulting signatures with disease, tissue, compound and gene perturbation

Caspase-8 Quickview QuickView is the default nextbio app, just type in CASP8 and then click quickveiw, it will give summaries of topranked correlations in several categories. Tissue, Disease, Compound and more. Body Atlas shows the gene expression levels in different tissues and cell lines Effectively mining such integrated information Correlation score is computed using rank-based enrichment algorithms

Caspase-8 Expression in Tissues and Cell Lines Gene expression level=2570 Median expression across all cell lines=1320 Gene expression level=448±21.7 Median expression across all tissues=495

Caspase-8 Expression in Cancers 353 invasive breast cancer samples vs normal breast There are over 200 studies investigating Caspase-8 mutation, copy number variation, methylation and altered expression linked to different cancers Genes are ranked by a score function that takes into account the differential expression compared to control, and the standard deviation Over 200 Caspase-8 correlated cancer studies found

Caspase-8 Expression and Compounds Perturbation Several studies have identified changes in caspase-8 expression linked to anticancer drug This will help you to find the connections between drugs, genes and diseases though the common gene expression changes

Caspase-8 Expression and Gene Perturbations The results are listed of genes whose perturbation influences Caspase-8. The top perturbed gene is PPARA 7 studies provided evidence that perturbing PPARA decreases caspase-8 expression based on RNA expression data. PPAR affects the expression of target genes involved in cell proliferation, cell differentiation, etc To learn more about how PPARA downregulate Caspase-8 expression, lets look at the experimental details of the supported studies. Here are the list of 7 supported studies ranking from highest to lowest correlation with caspase-8

Oncomine Oncomine is the world’s largest existing human cancer genomic database that covers 699 independent datasets and more than 80,000 samples. Burnham insititute has recently purchased premium version of Oncomine, which allow us to do cancer subtype analysis and clinical outcome analysis, which are not available in free version of oncomine

Cancer subtype analysis -- Tumor development --Cancer metastasis --Cancer treatments Tumor grade is not the same as the stage of a cancer

Disease Summary for CASP8 Threshold (Gene Rank): All Threshold (Fold Change) 2 Threshold (P-value): 1E-4 Data Type: Cell color is determined by the best gene rank percentile for the analyses within the cell.

CASP8 Expression in Chandran Prostate Grouped by Cancer Sample Site Primary Site Metastasis Lymph Node Metastasis Metastasis - Gland Metastasis - Liver Metastasis - Lung

CASP8 Expression in Bittner Renal Grouped by Stage Stage 0a (1) Stage I (137) Stage II (22) Stage III (31) Stage IV (20)

CASP8 Expression in Neale Multi-cancer Grouped by Cisplatin Response Status Cisplatin Non-responder (9) Cisplatin Responder (6)

Next I will briefly introduce using cancer drug resistance database to find the relationship of drug targets mutation and drug resistance based on drug profiling on cancer cell lines. In Cancer therapy, one of the challenge questions is drug resistance and one of the main reasons is drug target mutation. This CancerDR will be useful for designing effective cancer therapy and predicting mutations responsible for drug resistance in cancer.

148 anticancer drugs assayed in CCLE and COSMIC, which are targeting a wide range of therapeutic cancer targets 925 cell lines from different tissue origins are covered in CancerDR

Browsing Drug Targets

Browsing Mutants of Drug Targets Click to see the type of mutants for each target

Browsing Drug Profiling of Mutant Cell Line Drug profiling on CW2 cell line

Summary Nextbio results show that Caspase-8 expression changes but not much in comparing cancer vs. normal, changes with compound and gene perturbations Oncomine results show that Caspase-8 expression does not change much with tumor development in kidney cancer , does not change much with cancer metastasis in prostate cancer and Caspase-8 expression does not change much between cisplatin responders and non-responders No information about Caspase-8 was found in CancerDR. Instead, we found Caspase-3 has four mutants which have different drug sensitivity/resistance

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Example of Using Nextbio Results to Generate Research Hypothesis Gene expression sets from both SM7- and SM6- resistant cells show strong negative correlation with Gene expression set of MLL leukaemia cell line MV4-11 treated with DOT1L inhibitor. Hypothesis: aberrant expression of the gene targeted by inhibition of DOT1L contributes to resistance to SM6 and SM7

Caspase-8 Expression in Cancer Metastasis