Three new potential ovarian cancer biomarkers detected in human urine with equalizer bead technology.
OBJECTIVE
To examine whether urine can be used to measure specific ovarian cancer proteomic profiles and whether one peak alone or in combination with other peaks or CA125 has the sensitivity and specificity to discriminate between ovarian cancer pelvic mass and benign pelvic mass.


METHODS
A total of 209 women were admitted for surgery for pelvic mass at the Gynaecological Department at Rigshospitalet, Copenhagen. Of the women, 156 had benign gynaecological tumors, 13 had borderline tumors and 40 had malignant epithelial ovarian cancer. The prospectively and preoperatively collected urine samples were aliquotted and frozen at -80 degrees until the time of analysis. The urine was fractionated using equalizer bead technology and then analyzed with surface-enhanced laser desorption/ionization time-of-flight mass spectrometry. Biomarkers were purified and identified using combinations of chromatographic techniques and tandem mass spectrometry.


RESULTS
Benign and malignant ovarian cancer cases were compared; 21 significantly different peaks (p<0.001) were visualized using Mann-Whitney analysis, ranging in m/z values from 1,500 to 185,000. The three most significant peaks were purified and identified as fibrinogen alpha fragment (m/z=2570.21), collagen alpha 1 (III) fragment (m/z=2707.32) and fibrinogen beta NT fragment (m/z=4425.09). The area under the receiver operator characteristic curve (ROC AUC) value for these three peaks in combination was 0.88, and their ROC AUC value in combination with CA125 was 0.96.


CONCLUSIONS
This result supports the feasibility of using urine as a clinical diagnostic medium, and the ROC AUC value for the three most significant peaks in combination with or without CA125 demonstrates the enhanced prediction performance of combined marker analysis.
Petri
Anette Lykke
AL
Department of Gynaecology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark. alpetri@dadlnet.dk
Simonsen
Anja Hviid
AH
Yip
Tai-Tung
TT
Hogdall
Estrid
E
Fung
Eric T
ET
Lundvall
Lene
L
Hogdall
Claus
C
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001707:Biopsy, Needle; D018394:CA-125 Antigen / Q000032:analysis* / Q000235:genetics; D018450:Disease Progression; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007813:Laparotomy / Q000379:methods; D008875:Middle Aged; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000097:blood / Q000473:pathology* / Q000601:surgery / Q000652:urine; D010386:Pelvic Neoplasms / Q000097:blood / Q000473:pathology / Q000601:surgery / Q000652:urine; D011237:Predictive Value of Tests; D011336:Probability; D011379:Prognosis; D011446:Prospective Studies; D040901:Proteomics; D012372:ROC Curve; D018570:Risk Assessment; D012494:Sampling Studies; D012680:Sensitivity and Specificity; D018709:Statistics, Nonparametric
D014408:Biomarkers, Tumor; D018394:CA-125 Antigen