MCQ 1

Question 1

clinical proteomics definition

Answer 1

the application of proteomic technologies to investigate protein express differences in protein expression in clinically obttained samples.

Question 2

biomarker

Answer 2

a naturally occuring molecule, gene or charcateristic by which a particular pathological oor physiological process, disease etc can be identified. EXAMPLE: substance produced by a tumour

Question 3

current roadblocks to body fluid biomarker discovery

Answer 3

1. clinically relevant biomarkers exist in blood and body fluids in extremeley low concentration.
2. even MS/MRM (multiple reaction monitoring) do not have sufficient sensitivity or dynamic range to detect biomarkey of such low concentration.

Question 4

what is the current lowest concentrationa t which current mass sopec can detect at

Answer 4

10 nanograms/ml

Question 5

what are the new technologies and resources that have led to more possible biomarker discovery

Answer 5

1.advanced bionformatics
2.mass spec based profilling and identificiation
3.protein fractionation

Question 6

where are applications of tumour markers most useful

Answer 6

prediction of therapeutic response and monitoring of effectiveness of cancer therapy

Question 7

examples of use of tumour markers in prediction of therapeutic response

Answer 7

steroid hormone receptors and HER2 amplification in breast cancer
NOTE: very few markers have predictive power

Question 8

in what areas do tumour markers have limited use and whay

Answer 8

diagnosis: too low sensitivity and specificity to serve as diagnostic markers

prognosis: most biomarkers have prognostic value but low accuracy in prediction of therapeutic intervention

Question 9

tumour marker

Answer 9

any substance present in or produced by tumor itself or produced by host in response to a tumor that can be used to differentiate tumor from normal tissue, which could be detected in cells, tissue or body fluids.

Question 10

factors that are ideal for serelogical tumour marker

Answer 10

1. produced by tumour cells and enter the circulation
   2.presenta t low levels in the serum of healthy individulas and thsoe with benign disease but increase substantially in cancer patients
   3.easily quantifiable, inexpensive
2. present in detectable quantities at early/preclinical stage
   6.quantitative levels of the tumour martker reflect the tumour burden
3. high diagnostic sensitivity and sepcificity

Question 11

name three tumour markers in breast cancer

Answer 11

ER and PgR
HER2
CA 15-3

Question 12

what is CA125

Answer 12

tumour marker in ovarian cancer used in prognosis, reoccurence detection, monitoring therapy.

Question 13

whata re the phases of biomarker development in order

Answer 13

experimental design
discovery
qualification
verification
validation and clinical assay development

Question 14

what type of body fluids are excamined in the experimental design phase

Answer 14

serum, plasma, saliva, nipple aspirate fluid, urine, pancreatic juice

Question 15

analytic challenges posed in experimental design phase

Answer 15

complexity and depth of proteome, low relative abunance expected for spevcific markers

Question 16

proximal fluid

Answer 16

biofluid closer to or in direct contact with the site of disease

Question 17

why are proximal fluids favourable for bimarker discovery

Answer 17

they are local “sinks” for proteins/peptides secreted shed or leaked from diseased tissue therefore potential biomarkers are likely to be enriched here

Question 18

three sources for biomarker discover in breast cancer patienmtys

Answer 18

nipple aspitrate fluid
breast cyst fluid
ductal lavage

Question 19

what the discovery phase of biomarker dicovery entail?

Answer 19

first, the samples are made less complex through fractination
then tumour and non-tumour specimens are compared to generate hypotheses for clinical tests for detecting cancer.

Question 20

immunodepletion

Answer 20

the use of an antibody to remobve high abundamnt proteins from a mixture

Question 21

in general what are the two classes of protein microarray formats

Answer 21

1 forward phase arrays (FPA)
2 reverse phase array (RPA)