Biomarkers

Andrew McNaughtBME

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.

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

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 effectbiomarker 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

Uses

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

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.

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

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.

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.

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.

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

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.

• 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

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

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

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

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.

Work cited • http://stm.sciencemag.org/content/3/79/79ps14.abstr

act• http://www.liver-products.com/liver-diagnostic/liver-

biomarker.html• http://www.niehs.nih.gov/research/supported/sep/

2003/polymorf/• http://omicsonline.org/jmbdhome.php• http://www.ncbi.nlm.nih.gov/sites/entrez?

db=pubmed&term=%22Cancer%20Epidemiol%20Biomarkers%20Prev%20%22[Journal]

NIH. "Cancer Biomarkers." Biomarkers (2009): 1-5. Print