Proteomic approaches to tumor marker discovery.
BACKGROUND
Current tumor markers for ovarian cancer still lack adequate sensitivity and specificity to be applicable in large populations. High-throughput proteomic profiling and bioinformatics tools allow for the rapid screening of a large number of potential biomarkers in serum, plasma, or other body fluids.


OBJECTIVE
To determine whether protein profiles of plasma can be used to identify potential biomarkers that improve the detection of ovarian cancer.


METHODS
We analyzed plasma samples that had been collected between 1998 and 2001 from patients with sporadic ovarian serous neoplasms before tumor resection at various International Federation of Gynecology and Obstetrics stages (stage I [n = 11], stage II [n = 3], and stage III [n = 29]) and from women without known neoplastic disease (n = 38) using proteomic profiling and bioinformatics. We compared results between the patients with and without cancer and evaluated their discriminatory performance against that of the cancer antigen 125 (CA125) tumor marker.


RESULTS
We selected 7 biomarkers based on their collective contribution to the separation of the 2 patient groups. Among them, we further purified and subsequently identified 3 biomarkers. Individually, the biomarkers did not perform better than CA125. However, a combination of 4 of the biomarkers significantly improved performance (P < or =.001). The new biomarkers were complementary to CA125. At a fixed specificity of 94%, an index combining 2 of the biomarkers and CA125 achieves a sensitivity of 94% (95% confidence interval, 85%-100.0%) in contrast to a sensitivity of 81% (95% confidence interval, 68%-95%) for CA125 alone.


CONCLUSIONS
The combined use of bioinformatics tools and proteomic profiling provides an effective approach to screen for potential tumor markers. Comparison of plasma profiles from patients with and without known ovarian cancer uncovered a panel of potential biomarkers for detection of ovarian cancer with discriminatory power complementary to that of CA125. Additional studies are required to further validate these biomarkers.
Rai
Alex J
AJ
Department of Pathology, the Johns Hopkins University School of Medicine, Baltimore, Md 21287, USA.
Zhang
Zhen
Z
Rosenzweig
Jason
J
Shih
Ie-Ming
IeM
Pham
Thang
T
Fung
Eric T
ET
Sokoll
Lori J
LJ
Chan
Daniel W
DW
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood*; D018394:CA-125 Antigen / Q000097:blood; D005260:Female; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000097:blood / Q000175:diagnosis*; D040901:Proteomics; D012680:Sensitivity and Specificity
D014408:Biomarkers, Tumor; D018394:CA-125 Antigen