Integrated proteomic analysis of human cancer cells and plasma from tumor bearing mice for ovarian cancer biomarker discovery.
BACKGROUND
The complexity of the human plasma proteome represents a substantial challenge for biomarker discovery. Proteomic analysis of genetically engineered mouse models of cancer and isolated cancer cells and cell lines provide alternative methods for identification of potential cancer markers that would be detectable in human blood using sensitive assays. The goal of this work is to evaluate the utility of an integrative strategy using these two approaches for biomarker discovery.


RESULTS
We investigated a strategy that combined quantitative plasma proteomics of an ovarian cancer mouse model with analysis of proteins secreted or shed by human ovarian cancer cells. Of 106 plasma proteins identified with increased levels in tumor bearing mice, 58 were also secreted or shed from ovarian cancer cells. The remainder consisted primarily of host-response proteins. Of 25 proteins identified in the study that were assayed, 8 mostly secreted proteins common to mouse plasma and human cancer cells were significantly upregulated in a set of plasmas from ovarian cancer patients. Five of the eight proteins were confirmed to be upregulated in a second independent set of ovarian cancer plasmas, including in early stage disease.


CONCLUSIONS
Integrated proteomic analysis of cancer mouse models and human cancer cell populations provides an effective approach to identify potential circulating protein biomarkers.
Pitteri
Sharon J
SJ
Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
JeBailey
Lellean
L
Faça
Vitor M
VM
Thorpe
Jason D
JD
Silva
Melissa A
MA
Ireton
Reneé C
RC
Horton
Marc B
MB
Wang
Hong
H
Pruitt
Liese C
LC
Zhang
Qing
Q
Cheng
Kuang H
KH
Urban
Nicole
N
Hanash
Samir M
SM
Dinulescu
Daniela M
DM
D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism*; D045744:Cell Line, Tumor; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015151:Immunoblotting; D013058:Mass Spectrometry / Q000379:methods; D051379:Mice; D015233:Models, Statistical; D009368:Neoplasm Transplantation; D010051:Ovarian Neoplasms / Q000097:blood* / Q000378:metabolism*; D020543:Proteome; D040901:Proteomics / Q000379:methods*
D014408:Biomarkers, Tumor; D020543:Proteome