Tumor vascular proteins as biomarkers in ovarian cancer.
OBJECTIVE
This study aimed to identify novel ovarian cancer biomarkers and potential therapeutic targets through molecular analysis of tumor vascular cells.


METHODS
Immunohistochemistry-guided laser-capture microdissection and genome-wide transcriptional profiling were used to identify genes that were differentially expressed between vascular cells from human epithelial ovarian cancer and healthy ovaries. Tumor vascular markers (TVMs) were validated through quantitative real-time polymerase chain reaction (qRT-PCR) of immunopurified tumor endothelial cells, in situ hybridization, immunohistochemistry, and Western blot analysis. TVM expression in tumors and noncancerous tissues was assessed by qRT-PCR and was profiled using gene expression data.


RESULTS
We identified a tumor vascular cell profile of ovarian cancer that was distinct from the vascular profile of normal ovary and other tumors. We validated 12 novel ovarian TVMs. These were expressed by immunopurified tumor endothelial cells and localized to tumor vasculature. Select TVMs were found to be specifically expressed in ovarian cancer and were absent in all normal tissues tested, including female reproductive tissues with physiologic angiogenesis. Many ovarian TVMs were expressed by a variety of other solid tumors. Finally, overexpression of any one of three ovarian TVMs by vascular cells was associated with decreased disease-free interval (all P < .005).


CONCLUSIONS
We have identified for the first time the molecular profile of ovarian tumor vasculature. We demonstrate that TVMs may serve as potential biomarkers and molecular targets for ovarian cancer and a variety of other solid tumors.
Buckanovich
Ronald J
RJ
Center for Research on Reproduction and Women's Health, Abramson Family Cancer Research Institute, Department of Medicine Division of Hematology-Oncology, Philadelphia, PA, USA.
Sasaroli
Dimitra
D
O'Brien-Jenkins
Anne
A
Botbyl
Jeffrey
J
Hammond
Rachel
R
Katsaros
Dionysios
D
Sandaltzopoulos
Raphael
R
Liotta
Lance A
LA
Gimotty
Phyllis A
PA
Coukos
George
G
D014408:Biomarkers, Tumor / Q000032:analysis*; D002135:Calcium-Binding Proteins; D015815:Cell Adhesion Molecules; D003094:Collagen / Q000032:analysis / Q000235:genetics; D024161:Collagen Type XI / Q000032:analysis / Q000235:genetics; D005260:Female; D005455:Fluorescent Antibody Technique; D020869:Gene Expression Profiling; D006023:Glycoproteins / Q000032:analysis; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins / Q000032:analysis / Q000235:genetics; D009363:Neoplasm Proteins / Q000032:analysis*; D010051:Ovarian Neoplasms / Q000737:chemistry*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis / Q000235:genetics; D016133:Polymerase Chain Reaction; D018124:Receptors, Tumor Necrosis Factor / Q000032:analysis / Q000235:genetics
D014408:Biomarkers, Tumor; D002135:Calcium-Binding Proteins; D015815:Cell Adhesion Molecules; D024161:Collagen Type XI; C403518:EGFL6 protein, human; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D018124:Receptors, Tumor Necrosis Factor; C114997:STC2 protein, human; C114109:TNFRSF21 protein, human; D003094:Collagen