Use of reverse phase protein microarrays and reference standard development for molecular network analysis of metastatic ovarian carcinoma.
Cancer can be defined as a deregulation or hyperactivity in the ongoing network of intracellular and extracellular signaling events. Reverse phase protein microarray technology may offer a new opportunity to measure and profile these signaling pathways, providing data on post-translational phosphorylation events not obtainable by gene microarray analysis. Treatment of ovarian epithelial carcinoma almost always takes place in a metastatic setting since unfortunately the disease is often not detected until later stages. Thus, in addition to elucidation of the molecular network within a tumor specimen, critical questions are to what extent do signaling changes occur upon metastasis and are there common pathway elements that arise in the metastatic microenvironment. For individualized combinatorial therapy, ideal therapeutic selection based on proteomic mapping of phosphorylation end points may require evaluation of the patient's metastatic tissue. Extending these findings to the bedside will require the development of optimized protocols and reference standards. We have developed a reference standard based on a mixture of phosphorylated peptides to begin to address this challenge.
Sheehan
Katherine M
KM
United States Food and Drug Administration (FDA)-NCI Clinical Proteomics Program, Laboratory of Pathology, Center for Cancer Research, NCI, National Institutes of Health, Bethesda, MD, USA.
Calvert
Valerie S
VS
Kay
Elaine W
EW
Lu
Yiling
Y
Fishman
David
D
Espina
Virginia
V
Aquino
Joy
J
Speer
Runa
R
Araujo
Robyn
R
Mills
Gordon B
GB
Liotta
Lance A
LA
Petricoin
Emanuel F
EF
Wulfkuhle
Julia D
JD
D002277:Carcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D008967:Molecular Biology / Q000379:methods*; D009362:Neoplasm Metastasis / Q000473:pathology; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D010766:Phosphorylation; D040081:Protein Array Analysis / Q000379:methods*; D040901:Proteomics / Q000379:methods*; D012015:Reference Standards; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D015398:Signal Transduction
D010455:Peptides