Cancer Proteomic_AHBS 3274_latest.pptx

AHBS 3274 Molecular Cancer Research Proteomics in Cancer Research Asst. Prof. Dr. Izzuddin bin Ahmad Nadzirin Department of Biomedical Science Kulliyyah of Allied Health Sciences http://www.free-powerpoint-templates-design.com  An abnormal growth of cells caused...

AHBS 3274 Molecular Cancer Research Proteomics in Cancer Research Asst. Prof. Dr. Izzuddin bin Ahmad Nadzirin Department of Biomedical Science Kulliyyah of Allied Health Sciences http://www.free-powerpoint-templates-design.com  An abnormal growth of cells caused by multiple changes in gene expression or mutation Cancer?  Genomics Metabolomics Proteomics Transcriptomics Multi-Omics Multi-Omics approaches using patient samples have been used worldwide in translational research. A multi-Omics analysis is a comprehensive and integrated analysis of combined data generated from various omics approaches, including proteomics, genomics, transcriptomics, and metabolomics. Multi-Omics analyses can produce large-scale datasets compared to a single analysis, and provides valuable information on the pathophysiology of diseases caused by complex events, thereby making a significant contribution to the diagnosis of diseases and the development of treatments. Therefore, the continual use of Omics approaches that aggregates multiple Omics data sets will likely have a significant impact on translational research, including in cancer biology, and will likely be the basis for the study of various diseases going forward.  The term proteomics and proteome coined by Mark Willkins & his colleagues. Proteomics Study of the entire set of proteins expressed in a cell, tissue, or individual. Involves a wide range of processes such as protein expression profiling, modifications, structure, function, and protein-protein interactions. Technically, proteomics can be defined as a research field that involves the large-scale identification, characterization, and quantitation of proteins expressed in a cell line, tissue, or organism under given conditions  Results obtained from such tasks can be used to decipher disease processes, Proteomics provide diagnosis and prognosis of diseases, aid in drug development, and deliver the basis for biological discovery. Various techniques: 2-D PAGE Mass spectrometry Genomic database Bioinformatics Protein microarrays  Proteins are functional molecules in cells and represent important targets for the Proteomics therapeutic intervention. Impossible to accurately predict genes and their structures by genomic data and bioinformatics. Protein study can confirm the existence of a particular gene and characterize the protein expressed by the gene.  Protein expression and the expression level are not the direct reflection of the Proteomics mRNA levels and protein expression also subjects to post-translational modification. Therefore, a gene can express different types and amounts of proteins under different conditions. These varied phenotypes are responsible for the actual biological functions of a gene in cells. Proteomics is established to address these problems.  Expression proteomics Proteomics Structural Functional proteomics proteomics Steps in proteomic analysis Protein fractionation Digested proteins Protein extraction fractioned using gel LC-MS analysis Proteins electrophoresis extracted and Identification of purified from protein by LC-MS tissue or cell and proteome Protein digestion lysates by database centrifugation Proteins digested and using certain filtration enzymes (usually trypsin) Key Components of Current Proteomic Technology 2-D PAGE Begins with electrophoresis in the first dimension and then separates the molecules perpendicularly from the first to create an electropherogram in the second dimension Rotate 90o  It is an analytical technique that ionizes Mass chemical species and sorts the ions based spectrometry on their mass to charge ratio Used to identify proteins in a mixture MALDI-TOF, SELDI-TOF  Matrix-assisted laser desorption/ ionization (MALDI) is an ionization technique MALDI-TOF that uses a laser energy absorbing matrix to create ions from large molecules with minimal fragmentation. Applied to the analysis of biomolecules (such as DNA, proteins) and various organic molecules (such as polymers), which tend to be fragile and fragment when ionized by more conventional ionization methods. Time-of-flight mass spectrometry (TOFMS) is a method of mass spectrometry in which an ion's mass-to-charge ratio is determined by a time of flight measurement.  MALDI/TOF Mass Spectrometer Your Picture Here Your Picture Here Content Here Director You can simply impress your audience and add a unique zing and appeal to your Presentations. Name Here Name Here  Surface-enhanced laser desorption/ionization. SELDI-TOF Extension of MALDI-TOF. In MALDI, the sample is mixed with a matrix material and applied to a metal plate before irradiation by a laser, whereas… In SELDI, proteins of interest in a sample become bound to a surface before MS analysis. The sample surface is a key component in the purification, desorption, and ionization Reverse translational research strategy.  System biology - understand cell- pathways, network, and complex Applications interaction. Biological processes - characterize sub- proteomes such as protein complexes, cellular machines, organelles Biomarkers - discovery of disease (serological, urine, other biological fluids) - diagnostics, treat patients, monitor therapies Drug targets - evaluate toxicity & other  The protein composition may be associated Biomarkers with disease processes in the organism and thus have potential utility as diagnostic markers. Proteins are closer to the actual disease process, in most cases, than parent genes. Proteins are ultimate regulators of cellular function. Biomarkers Most cancer markers are proteins. The vast majority of drug targets are proteins. Individual biomarkers are not sufficient for accurate disease detection. Panel of biomarkers should be established. Biomarkers ASimple cancer biomarker PowerPoint Presentation refers to that Simple PowerPoint is Presentation indicative ofPresentation Simple PowerPoint the presence ofPresentation Simple PowerPoint cancer in the body Important tool for cancer detection & monitoring You can simply impress your audience and add a unique zing and appeal to your Presentations. Easy to change colors, photos Proteins used as and Text. You can simply impress your audience and add a unique zing and appeal to biomarkers (HER-2, your Presentations. EGFR) Application of Proteomics Simple PowerPoint Presentation in Cancer Research - Fundamental role of cancer Simple PowerPoint Presentation therapeutics Simple PowerPoint Presentation is inhibition of aberrant Simple PowerPoint Presentationcell growth. - Proteomics – discovery of specific biomarkers for cancer growth. You can simply impress your audience and add a unique zing and appeal to your Presentations. Easy to change colors, photos and Text. You can simply impress your Cancer growth audience and add a unique zing and appeal to your Presentations. Human breast canc  PYCR2 is a crucial enzyme in proline biosynthesis, which was shown as the most significantly altered amino acid metabolism by metabolomics profiling in HCC. ADH1A – metabolises xenobiotic compounds including alcohol, retinol, aliphatic alcohols, hydroxysteroids, and lipid peroxidation products – classic liver function Downregulation may lead to dysregulated xenobiotics metabolism and facilitate hepatocellular carcinoma progression. Relative abundance of PYCR2 and ADH1A between tumor and non- tumor tissues (T test) as well as across proteomic subgroups (ANOVA). (Gao et al. 2019) Application of Proteomics Simple PowerPoint Presentation in Cancer Research - Metastasis is a severe Simple PowerPoint Presentation Simple PowerPoint obstacles Presentation for the successful Simple PowerPoint development Presentation of therapeutics – common feature of malignant cancer. - However, the precise mechanism by which the metastatic cascade occurs is You can simply impress your audience and add a unique zing andnot appeal toclearly your defined. Presentations. Easy to change colors, photos and Text. You can simply impress your audience and add a unique zing and appeal to your Presentations. Metastasis Human breast canc Mice treated with dexamethasone (glucocorticoid to treat side effects of breast cancer) – activates glucocorticoid receptor. Then transplanted with cancerous cells. Average radiance – the extend of metastasis. Also indicated in the bioluminescence imaging. Overall survival decreased in dexamethasone-treated mice. (Obradovic et al. 2019) (Kwon et al. 2021)  Identification of specific biomarker for Drug specific cancers is the fundamental in drug discovery. Discovery Identifying specific proteins that drive tumor growth, survival, and metastasis is crucial for developing targeted therapies with enhanced efficacy and reduced side effects. Drug screening can target specific these biomarkers.  Allows characterisation and Drug classification of the patient populations who are most likely to respond to Discovery targeted therapies. E.g. Tyrosine kinase inhibitor: Blocks activity of tyrosine kinases, enzymes involved in cell signaling pathways implicated in cancer. Imatinib (Gleevec) targeting BCR-ABL in chronic myeloid leukemia and EGFR inhibitors like erlotinib (Tarceva) and gefitinib (Iressa) in non-small cell lung cancer.  Approach to tailor disease prevention Precision and treatment based on different proteomic, genomics, environments Drug and lifestyles. In cancer care, this involves selecting treatments that are most likely to be effective based on the unique characteristics of the patient's tumor. Analysis shall be done on individual patient samples to screen for activation of key signalling networks.  By comparing protein expression Precision profiles between tumor samples and normal tissues, proteomics can identify Drug aberrantly expressed proteins that serve as potential therapeutic targets by giving mono- or combination-drug therapy. Follow-up analysis to identify signalling reprogramming after treatment (resistance), and redirect treatment to the new signalling.  Proteomics Data Repositories – some examples https://www.nextprot.org/ https://www.ebi.ac.uk/pride/ https://proteopedia.org/wiki/index.php/Main_Page https://www.proteinatlas.org/ https://www.rcsb.org/ https://string-db.org/cgi/input?sessionId=bgDTi7LcQpU7&input_page_show_search=on  References Gao, et al. (2019). Integrated Proteogenomic Characterization of HBV-Related Hepatocellular Carcinoma. Cell, 179, 561-577. Obradovic, et al. (2019). Glucocorticoids promote breast cancer metastasis. Nature, 567, 540–544. Kwon, et al. (2021). Application of Proteomics in Cancer: Recent Trends and Approaches for Biomarkers Discovery. Frontiers in Medicine, 8, 747333.