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Biomarkers
Andrew McNaught
BME
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 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
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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.
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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/liverbiomarker.html
• 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]
NIH. "Cancer Biomarkers." Biomarkers (2009): 1-5. Print