Transcript 3 MBFiehn_Seattle_October_2010_Part_3

Hormone receptor @ grade 2
60
% of patients
Methods
50
40
30
double pos.
ER+ PR+
HER2-
grade 1
grade 2
grade 3
20
10
triple pos.
ER+ PR+
HER2+
0
E+P+H-
E+P+H+
E+P-H-
Estrogen positive
E+P-H+
E-P+H-
E-P+H+
E-P-H-
Estrogen negative
E-P-H+
Results
Metabolic phenotype of HER2 +/- grade 2 tumors
Grade 2
E+P+H- (69) Vs E+P+H+ (19)
Can we identify unknowns?
Methods
5-methyluracil
3-methyluracil
1-methyluracil…
then: CI_GCT
0 100
C5H6N2O2
189.9976
147.0657
%
241.1024
M-15
257.1409
M+H
275.1654
Madd
200
m/z
PubChem
ChemSpider
CSLS DB
Conclusion
Conclusion
 Metabolomics is mature for discovery research. ~15% CV.
More than one platform is needed due to chemical diversity.
Databases are essential.
 Once new biomarker panels are established,
clinical validation could use less sophisticated techniques.
 Breast cancer tumors vastly differ metabolically from normal to grade 1-3
Triple negative tumors (ER-,PR-,HER2-) were mostly grade 3.
 Metabolomics yields novel hypotheses on clinically relevant questions:
Triple negative tumors have dysregulation of several metabolic modules:
amino acids, nucleotide, membrane lipids and energy metabolism,
plus salicylate and oligosaccharide metabolism.
 Note: steady state levels may not change (pyruvate, free fatty acids,
glutamine) although metabolic fluxes may be higher (as indicated in endpoint
accumulations or products). More mechanistic insights by stable isotope studies.
Thanks to fiehnlab.ucdavis.edu !
Thanks to MetaCancer collaborators , PI Prof Carsten Denkert,
Charite Berlin, Germany
European Union FP7 Health-2007-2.1.4.1 project 200327
NIH R01 ES013932, R01 DK078328, RC2 GM092729, R01 HD058556