Evaluation of the novel serum markers B7-H4, Spondin 2, and DcR3 for diagnosis and early detection of ovarian cancer.
OBJECTIVE
Early detection through regular screening could significantly reduce mortality from ovarian cancer. Advances in biomarkers and imaging continue to improve the sensitivity and specificity of cancer detection, but further improvements are still needed. In this study, we identified and evaluated three new serum biomarkers that may be used to improve detection of ovarian cancer.


METHODS
Through genomic analysis, we identified B7-H4, Spondin 2, and DcR3 as over-expressed genes in ovarian cancer tissues. Sensitive sandwich ELISAs were developed to analyze the level of these novel markers in 68 serum samples from patients with ovarian cancer (16 early stage, 52 late stage) and 108 control samples, and 20 healthy women from which two serum samples were collected 1 year apart. CA125 levels were measured in all samples.


RESULTS
Markers were evaluated for their ability to identify clinical disease. The three novel markers and CA125 were elevated in serum of ovarian cancer patients as compared to normal controls. B7-H4 showed the highest specificity, with the lowest frequency of elevation in all control groups. When all cases were compared against all controls, CA125, Spondin 2, B7-H4, and DcR3 showed areas under the ROC curve of 0.87, 0.78, 0.74, and 0.71, respectively. CA125 and B7-H4 showed the best diagnostic performance for early-stage, with AUCs of 0.90 and 0.80, respectively.


CONCLUSIONS
This study demonstrates that B7-H4, Spondin 2, and DcR3 are promising new ovarian cancer markers that may improve early detection of cancer when used in combination with traditional diagnostic tests.
Simon
Iris
I
diaDexus, Inc., 343 Oyster Point Blvd., South San Francisco, CA 94080, USA.
Liu
Yan
Y
Krall
Kirstin L
KL
Urban
Nicole
N
Wolfert
Robert L
RL
Kim
Nam W
NW
McIntosh
Martin W
MW
D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry; D018122:B7-1 Antigen / Q000097:blood*; D014408:Biomarkers, Tumor / Q000097:blood*; D018394:CA-125 Antigen / Q000097:blood; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D016326:Extracellular Matrix Proteins / Q000097:blood*; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D051379:Mice; D008807:Mice, Inbred BALB C; D009363:Neoplasm Proteins / Q000097:blood*; D010051:Ovarian Neoplasms / Q000097:blood* / Q000175:diagnosis; D053323:Receptors, Tumor Necrosis Factor, Member 6b / Q000097:blood*; D060907:V-Set Domain-Containing T-Cell Activation Inhibitor 1
D000911:Antibodies, Monoclonal; D018122:B7-1 Antigen; D014408:Biomarkers, Tumor; D018394:CA-125 Antigen; D016326:Extracellular Matrix Proteins; D009363:Neoplasm Proteins; D053323:Receptors, Tumor Necrosis Factor, Member 6b; C122166:SPON2 protein, human; C505911:TNFRSF6B protein, human; D060907:V-Set Domain-Containing T-Cell Activation Inhibitor 1; C475826:VTCN1 protein, human