L6: Biomarkers in clinical studies Flashcards
define biomarkers
a defined characteristic that is measured as an indicator of:
1. a normal biological process
2. pathogenic process
3. response to (therapeutic) intervention
are biomarkers the same as symptoms?
no. biomarkers are more quantitative
state the 7 categories of biomarkers
hint: dm ppp and ss
- diagnostic biomarker
- monitoring biomarker
- pharmacodynamic biomarker
- predictive biomarker
- prognostic biomarker
- safety biomarker
- susceptibility/risk biomarker
what is diagnostic biomarkers? +examples
used to identify individuals WITH the disease/condition OR to define a subset of the disease
eg. blood sugar in diabetes
eg. ejection failure in heart failure
what is monitoring biomarker? +examples
- biomarker measured repeatedly and used to detect a change in the degree of disease
- can also be used to indicate toxicity or assess safety or provide evidence of exposure to eg. medical products
eg. PSA in prostate cancer; CA-125 in ovarian cancer
what is a predictive biomarker? example?
-used to identify indivs who are MORE LIKELY than indivs without biomarker to experience favourable/unfavourable effect from a specific intervention/exposure
- usually checked before giving patient treatment to predict gauge likelihood of response
eg. EGFR mutation in lung cancer for anti-EGFR drugs
eg. PD1 expression in tumour for anti-PD1 therapy
what is prognostic marker? example?
used to identify likelihood of CLINICAL EVENT, DISEASE recurrence or progression.
eg. BRCA1/2 mutation in breast cancer patients for likelihood of second breast cancer
eg. Ch17p deletions in Chronic lymphoblastic leukemia for likelihood of death
eg. PSA in prostate cancer -> likelihood of cancer progression
what is safety biomarker? + 2 examples
used to indicate the presence/extent of TOXICITY related to an intervention/exposure
eg. hepatic aminotransferase in hepatotoxicity
eg. serum creatinine in nephrotoxicity
what is susceptibility/risk biomarker?
biomarker that indicate the POTENTIAL for developing disease/medical condition or sensitivity to an exposure in an indiv without clinically apparent disease or medical condition –> * no symptom for disease yet
eg. BRCA1/2 mutation -> risk of getting breast cancer
eg. APOE gene variations-> risk of earlier onset of Alzheimers
eg. infection of HPV subtypes in likelihood for cervical cancer
whats the difference between susceptibility and diagnostic marker?
diagnostic markers once present = 100% have disease
susceptibility markers not 100%, just indicative of POTENTIAL
difference between diagnostic and monitoring biomarker
diagnostic: IDENTIFIES disease in individuals; done once
monitoring: measured repeated over a period to detect CHANGE IN DEGREE/extent of disease
difference between predictive and prognostic biomarker
predictive: to determine likelihood of patient having favourable/unfavourable effects from intervention/drug
prognostic: identify likelihood of clinical event (death, disease recurrence or progression)
what is a pharmacodynamic marker? example?
used to show that a biological response has occurred in individual who has received intervention
eg. blood pressure in hypertension patients treated with anti-ypertensives
eg. viral load in covid patients
can a marker fall into more than 1 category?
yes
what kind of marker is blood pressure?
diagnostic, monitoring, pharmacodynamic marker
methods for cancer diagnosis [6]
- self examination
- blood/urine screening
- biopsy
- x-rays, CT scans, MRI scans, PET scans and ultrasound
- molecular diagnostic tests
- next gen sequencing
how is breast cancer diagnosed? [3]
- self-examination
- cytological analysis [get a breast tissue and analyse
- mammography
what are double minute chromosomes?
they are derived from chromosomal segments that have broken loose from original sites and have been replicated repeatedly as extrachromosomal genetic elements
what is a homogeneously staining region (HSR)?
when a marker gene gets amplified, it can cause an entire stretch of chromosome to stain the same
what is FISH?
in situ hybridisation of genes along chromosomes –> used to get a physical mapping of genes on chromosome
cancer can manifest itself through abnormalities in chromosomes, such as:
- inversion
- deletion
- translocation
- aneuploidy [change in number of chromosomes]
can cancer be diagnosed through histopathology?
yes
differentiate hyperplasia and dysplasia
hyperplasia: growth contain normal cells in excessive numbers
dysplasia: cells w abnormal appearance eg. nuclear size and shape
how are oncogenes detected? [2] compare the 2.
via immunoprecipitation/western blot and immunohistochemistry
both can detect proteins.
immunoprecipitation/western blot can show molecular weight of protein
immunohistochem: cannot see molecular weight but can see localisation changes in tissue [to validate that DNA/protein expression led to disease as it is not alws the case]
