Biomarkers

Biochimistry

2. Definition
Biomarkersarethemeasuresusedtoperformaclinicalassessmentsuchasblood
pressureorcholesterollevelandareusedtomonitorandpredicthealthstatesin
individualsoracrosspopulationssothatappropriatetherapeuticinterventioncanbe
planned.
Biomarkersmaybeusedtoassessthehealthordiseasestateofanindividual.
Generally,Biomarkercanbedefinedasacharacteristicthatisobjectivelymeasured
andevaluatedasanindicatorofnormalbiologicalprocesses,pathogenicprocesses,
orpharmacologicresponsestoatherapeuticintervention.

3. WHO has stated that a true definition of biomarkers includes "almost any measurement
reflecting an interaction between a biological system and a potential hazard, which may
be chemical , physical, or biological. The measure response may be functional and
physiological, biochemical at the cellular level, or a molecular interaction" Examples of
biomarkers include everything from pulse and blood pressure through basic chemistries
to more complex laboratory tests of blood and other tissues.
In medicine, a biomarker is a measurable indicator of the severity or presence of some
disease state.
For example, body temperature is a well-known biomarker for fever. Blood pressure is
used to determine the risk of stroke. It's also widely known that cholesterol values are a
biomarker and risk indicator for coronary and vascular disease, and that C-reactive
protein (CRP) is a marker for inflammation.

4. A wide range of biomarkers are used today . every biological system has it's own
specific biomarkers.
Generalhealthcheckmayincludeassessmentofbloodpressure,heartrate,
cholesterol,triglyceridesandfastingglucoselevels.Bodymeasurementsuchas
weight,bodymassindex(BMI),andwaist-to-hipratioareroutinelyusedfor
assessingconditionssuchasobesityandmetabolicdisorders.

5. Disease related biomarkers and drug-related biomarkers
It'snecessarytodistinguishbetweendisease-relatedanddrug-relatedbiomarkers.
Disease-relatedbiomarkersgiveanindicationoftheprobableeffectoftreatmenton
patient(riskindicatororpredictivebiomarkers),ifadiseasealreadyexists
(diagnosticbiomarkers),orhowsuchadiseasemaydevelopinanindividualcase
regardlessofthetypeoftreatment(prognosticbiomarker).Predictivebiomarkers
helptoassessthemostlikelyresponsetoaparticulartreatmenttype,while
prognosticmarkersshowstheprogressionofdiseasewithorwithouttreatment.In
contrast,drug-relatedbiomarkersindicatewhetheradrugwillbeeffectiveina
specificpatientandhowthepatient'sbodywillprocessit.
Inthepast,biomarkerswereprimarilyphysiologicalindicatorssuchasblood
pressureorheartrate.Morerecently,biomarkerisbecomingasynonymfor
molecularbiomarker,suchaselevatedprostatespecificantigenasamolecular
biomarkerforprostatecancer.

6. Biomarker Requirements
1.In order to use a biomarker for diagnostics, the sample material must be as easy
to obtain as possible.
2.The speed with a result is obtained from the biomarker test is critical (rapid test).
3.Biomarker must be accurate and as easy to carry out as possible.
4.A biomarker for clinical use needs good sensitivity and specificity e.g ≥ 0.9.

7. Biomarker Classification
A-Based on their characteristics
1-Imaging biomarkers (CT, PET, MRI)
2-Molecular biomarkers ( biophysical properties in biological samples)
B-Classified based on their application
1-Physiological biomarker e.g pregnancy test
2-Diagnostic biomarkers e.g Cardiac troponin for the diagnosis of myocardial infraction
3-Staging of disease biomarkers e.g Chronic kidney disease ( End stage renal failure )
4-Disease prognosis biomarkers e.g Cancer biomarkers
5-Biomarkers for monitoring the clinical response to an intervention
e.g HbA1C for anti-diabetic treatment

9. Technical Validation of Biomarker
Accuracy ( agreement with a reference)
Precision ( repeatability, reproducibility)
Limit of Detection ( sensitivity )
Interference , Cross-reactivity ( specificity)
Sample preparation / conditions.
Performance around the cut-off
Potential for carryover, cross-hybridization

10. Biomarker
Advantages Disadvantages
Objective assessment
Precision of measurement
Reliable, validity can be
established.
Less biased than questionnaires
Disease mechanism often
studied.
Homogeneity of risk or disease
Timing is critical
Expensive ( cost for analysis)
Storage ( longevity of samples)
Laboratory errors
Normal range difficult to
establish
Ethical responsibility