1. Biomarkers Andrew McNaught BME

2. What is a biomarker? Gives us the ability to analyze organ function, diagnose diseases in a non-invasive way. Biomarkers can be any molecule (organic or inorganic) that acts at the test subject while the patient is the host to a biological process. Biomarkers can be tested from bodily fluids (blood, urine) or from tissues.

3. Importance Biomarkers give scientists and doctors the ability to ‘work backwards’ and asses organ function. Cancer biomarkers can identify genetic variations or mutations as well as changes in gene or protein expression that can be linked to a disease state or a response to a medical intervention

4. Definition A measurement reflecting a biological system and an environmental agent that can be chemical, physical or biological biomarker of exposure: an exogenous substance or its metabolite or the product of an interaction between a xenobiotic agent and some target molecule or cell that is measured in a compartment within an organism; biomarker of effect **biomarker of effect: a measurable biochemical, physiological, behavioural or other alteration within an organism that, depending upon the magnitude, can be recognized as associated with an established or possible health impairment or disease; ** biomarker of susceptibility - an indicator of an inherent or acquired ability of an organism to respond to the challenge of exposure to a specific xenobiotic substance. http://www.inchem.org/documents/ehc/ehc/ehc155.htm#SectionNumber:1.1

5. Uses Biomarkers can be used to: confirm diagnosis of acute or chronic disease assess the effectiveness of treatment evaluate the prognosis of individual cases.

6. Biomarkers in Cancer Detection The Early Detection Research Network has put growing focus on discovering and validating biomarkers in their use to diagnose cancer in its early stages. Many patients are diagnosed in late stages of cancer and it may be too late. Could be a huge breakthrough for science if this non-invasive method can test for cancer.

7. Brain Cancer National Cancer Institute study on finding improved therapies for adult glioma. (most deadly brain tumor) This study's purpose is to find molecular features of tumors, immune factors and genetic polymorphisms as biomarkers. Purpose- – Specific therapies are more beneficial to patients that display specific genetic, immunological and tumor characteristics. – University of California San Francisco – Funded amount – $186,000

8. Serum test Serum biomarkers are produced by body organs or tumors and they measure the antigens on cells’ surfaces. When detected in high amounts in the blood, they can be suggestive of tumor activity. Serum biomarkers are non-specific because organs they can be produced by organ systems as well.

9. PSA PSA is produced by normal prostate function in small amounts but a large amount is indicative of prostate cancer. This is one of the most widely used biomarkers in use today.

10. Ovarian cancer Cancer agent 125 can be a biomarker of ovarian cancer or indicator. It has low sensitivity and specificity. Levels of this agent can be high in patients with pancreatic, kidney or liver disease.

11. Carinoembryonic antigen (CEA) Another biomarker that is elevated in people with breast, lung and pancreatic cancer. But, it can be elevated by other factors than cancer such as smoking. After patients have surgery for colon cancer, CEA is an effective way to evaluate how successful surgery was

12. Biomarkers for Parkinsons Disease Parkinson's disease occurs when a persons brain does not naturally produce enough dopamine to have healthy brain function. – The diminishing amount of dopamine neurotransmission is a biochemical marker for Parkinsons – NIH did a study to show the relationship between purine and dopamine in cerebrospinal fluid. – The ratio between (xanthine/homovanillic acid) should be 13.1 +- 5.5 – In patients with parkinsons, the ratio was raised to 17.4 at the initial check and 19.7 at a second check 24 months later. – The ratio raises as the disease severity raises.

13. These biomarkers used to detect this ratio can be very beneficial. – Earlier prognosis – Earlier treatment – Treatment depending on how severe it is – Track the disease with more precision – Test the effectiveness of new treatment

14. Predicting Liver Cancer Some Proteins which might be used as Liver Biomarkers Lectin-reactive alpha fetoprotein (AFP-L3) Des-gamma-carboxy-prothrombin (DCP) ER6Q Vimentin actin alpha 1 skeletal muscle protein hMFAP 4 tropomyosin PTGES 2 amyloid P component transgelin calponin 1 homo sapiens p20 protein 17 kDa myosin light chain H chain H Igg B12 prolyl 4-hydroxylase beta subunit methylenetetrahydrofolate dehydrogenase 1 PRO2619 aldehyde dehydrogenase 1 fibrinogen alpha chain preproprotein fructose-bisphosphate aldolase B argininosuccinate synthetase Eefla2 AT P 5 Al alpha-2 actin regucalcin serum albumin mitochondrial malate dehydrogenase mitochondrial acetoacetyl-CoA thiolase

15. Liver biomarkers Vitamin D-binding protein and liver fatty acid binding protein have been identified as biomarkers for liver toxicity. Using these biomarkers would allow patients to avoid a liver biopsy and assessing 4 common chronic liver diseases. – Hepatitis C – Hepatitis B – Non alcoholic fatty liver diseases and – Alcoholic fatty liver diseases

16. NIH New biomarker for kidney toxicology that could lead to better and faster diagnosis of kidney injury. Found nine new gene variants, also known as single nucleotide polymorphisms, associated with an increased risk of myocardial infarction or heart attack Expression of DNA Repair Genes is Sensitive Marker for Oxidative Stress Gene-Environment Interaction: Effect of Polymorphisms on Biomarkers in Coal Miners

17. Future In the future: Biomarkers will be used as a significant prognosis tool to determine if a patient has a disease. Also I see a ‘one test’ suits all- one blood test will determine if someone has any number of diseases.

18. Work cited http://stm.sciencemag.org/content/3/79/79ps14.abstr act http://stm.sciencemag.org/content/3/79/79ps14.abstr act http://www.liver-products.com/liver-diagnostic/liver- biomarker.html http://www.liver-products.com/liver-diagnostic/liver- biomarker.html http://www.niehs.nih.gov/research/supported/sep/20 03/polymorf/ http://www.niehs.nih.gov/research/supported/sep/20 03/polymorf/ http://omicsonline.org/jmbdhome.php http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed &term=%22Cancer%20Epidemiol%20Biomarkers%20Pr ev%20%22[Journal] http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed &term=%22Cancer%20Epidemiol%20Biomarkers%20Pr ev%20%22[Journal NIH. "Cancer Biomarkers." Biomarkers (2009): 1-5. Print