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Abstract
BACKGROUND:
Biomarkers play critical roles in early detection, diagnosis and monitoring of therapeutic outcome and recurrence of cancer. Previous biomarker research on ovarian cancer
(OC) has mostly focused on the discovery and validation of diagnostic
biomarkers. The primary purpose of this study is to identify serum
biomarkers for prognosis and therapeutic outcomes of ovarian cancer.
EXPERIMENTAL DESIGN:
Forty
serum proteins were analyzed in 70 serum samples from healthy controls
(HC) and 101 serum samples from serous OC patients at three different
disease phases: post diagnosis (PD), remission (RM) and recurrence (RC).
The utility of serum proteins as OC biomarkers was evaluated using a
variety of statistical methods including survival analysis.
RESULTS:
Ten
serum proteins (PDGF-AB/BB, PDGF-AA, CRP, sFas, CA125, SAA, sTNFRII,
sIL-6R, IGFBP6 and MDC) have individually good area-under-the-curve
(AUC) values (AUC = 0.69-0.86) and more than 10 three-marker
combinations have excellent AUC values (0.91-0.93) in distinguishing
active cancer
samples (PD & RC) from HC. The mean serum protein levels for RM
samples are usually intermediate between HC and OC patients with active cancer
(PD & RC). Most importantly, five proteins (sICAM1, RANTES, sgp130,
sTNFR-II and sVCAM1) measured at remission can classify, individually
and in combination, serous OC patients into two subsets with
significantly different overall survival (best HR = 17, p<10(-3)).
CONCLUSION:
We
identified five serum proteins which, when measured at remission, can
accurately predict the overall survival of serous OC patients,
suggesting that they may be useful for monitoring the therapeutic
outcomes for ovarian cancer.
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