(1)  Can we identify metabolites or metabolic pathways
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(1) Can we identify metabolites or metabolic pathways that are associated with breast cancer clinical parameters?. Alex-CIS-GCTOF MS w/ BinBase: 470 detected compounds 161 known metabolites, 309 without identified structure. grade2. grade1. Partial Least Square (multivariate stats).

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Results

(1) Can we identify metabolites or metabolic pathways that are associated with breast cancer clinical parameters?

Alex-CIS-GCTOF MS w/ BinBase: 470 detected compounds

161 known metabolites, 309 without identified structure.

grade2

grade1

Partial Least Square (multivariate stats)

Results

grade3

grade1

grade3

breast adipose

grade2


Results

Grade n1  23 tumors show differential up-regulation inPentose Phosphate Pathway, nucleotides, amino acids, arachidonic acid (but not free fatty acids, gln)

Results

production of NADPH, ribose units

production of DNA, RNA


Results

Grade n1  23 tumors show differential up-regulation inPentose Phosphate Pathway, nucleotides, amino acids, arachidonic acid (but not free fatty acids, gln)

Amino acids

Amino acids

citrate

glu

b-ala

n 1 2 3 grade

n 1 2 3 grade

Results

malate

lactate

n 1 2 3 grade

n 1 2 3 grade

C20:4

2HOglutarate

IDH1?

n 1 2 3 grade

n 1 2 3 grade


Results

Can we validate biomarkers in a fully independent study?Cohort 2 (113 patients)

Results


Results

Matej Orešič et al. (subm.)

Can we validate lipidomic biomarkers in a fully independent study?Cohort 2 (113 patients)

Results


Results

Orešič et al. (subm)

Can we validate lipidomic biomarkers in a fully independent study? Immunohistochemistry on tissue slides.

Results


Results

Can we get biochemical maps of differential regulation for hormone receptor status?

Methods

  • Up to 20% of the identified metabolites lack enzyme annotations.

  • Metabolic endpoint metabolites accumulate more than intermediates. ‘Comprehensive maps’ do not work.


Results

Can we get biochemical maps of differential regulation for hormone receptor status?

Methods

  • Up to 20% of the identified metabolites lack enzyme annotations.

  • Metabolic endpoint metabolites accumulate more than intermediates. ‘Comprehensive maps’ do not work.


Results

Chemical and biochemical mapping of metabolomic results

Methods


Results

Grade 1 tumors vs normal

Results

Red nodes: up-regulated in tumors at p<0.05, size ~ x-fold

Blue nodes: down-regulated in tumors at p<0.05, size~x-fold

Red edges: enzyme substrate/product in KEGGRpair DB

Green edges:chemical similarity > 0.7


Results

Hormone receptor @ grade 3

single neg.

ER+ PR+

HER2-

% of patients

Methods

triple neg.

ER- PR-

HER2-

Estrogen positive

Estrogen negative


Results

Metabolic phenotype of triple negative tumorsPatients without Estrogen, Herceptin neu2, Progesteron receptor

Results


Results

Hormone receptor @ grade 3

% of patients

Methods

triple neg.

ER- PR-

HER2-

double neg.

ER- PR-

HER2+

Estrogen positive

Estrogen negative


Results

Effect of HER2 status on metabolic phenotype of triple negative tumors

Results


Results

Hormone receptor @ grade 2

double pos.

% of patients

ER+ PR+

HER2-

Methods

triple pos.

ER+ PR+

HER2+

Estrogen positive

Estrogen negative


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