Measurement of phospholipids may improve diagnostic accuracy in ovarian cancer.
BACKGROUND
More than two-thirds of women who undergo surgery for suspected ovarian neoplasm do not have cancer. Our previous results suggest phospholipids as potential biomarkers of ovarian cancer. In this study, we measured the serum levels of multiple phospholipids among women undergoing surgery for suspected ovarian cancer to identify biomarkers that better predict whether an ovarian mass is malignant.


RESULTS
We obtained serum samples preoperatively from women with suspected ovarian cancer enrolled through a prospective, population-based rapid ascertainment system. Samples were analyzed from all women in whom a diagnosis of epithelial ovarian cancer (EOC) was confirmed and from benign disease cases randomly selected from the remaining (non-EOC) samples. We measured biologically relevant phospholipids using liquid chromatography/electrospray ionization mass spectrometry. We applied a powerful statistical and machine learning approach, Hybrid huberized support vector machine (HH-SVM) to prioritize phospholipids to enter the biomarker models, and used cross-validation to obtain conservative estimates of classification error rates.


RESULTS
The HH-SVM model using the measurements of specific combinations of phospholipids supplements clinical CA125 measurement and improves diagnostic accuracy. Specifically, the measurement of phospholipids improved sensitivity (identification of cases with preoperative CA125 levels below 35) among two types of cases in which CA125 performance is historically poor - early stage cases and those of mucinous histology. Measurement of phospholipids improved the identification of early stage cases from 65% (based on CA125) to 82%, and mucinous cases from 44% to 88%.


CONCLUSIONS
Levels of specific serum phospholipids differ between women with ovarian cancer and those with benign conditions. If validated by independent studies in the future, these biomarkers may serve as an adjunct at the time of clinical presentation, to distinguish between women with ovarian cancer and those with benign conditions with shared symptoms and features.
Frantz Biomarkers, LLC, Mentor, Ohio, USA.
Lian
L
Shan
Y Ann
YA
Chen
Lorelei
L
Davis
Gang
G
Han
Weiwei
W
Zhu
Ashley D
AD
Molina
Hector
H
Arango
James P
JP
LaPolla
Mitchell S
MS
Hoffman
Thomas
T
Sellers
Tyler
T
Kirby
Santo V
SV
Nicosia
Rebecca
R
Sutphen
D014408:Biomarkers, Tumor / Q000097:blood; D018394:CA-125 Antigen / Q000097:blood; D000077216:Carcinoma, Ovarian Epithelial; D005260:Female; D006801:Humans; D008875:Middle Aged; D008954:Models, Biological; D009375:Neoplasms, Glandular and Epithelial / Q000097:blood* / Q000145:classification / Q000175:diagnosis* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000097:blood* / Q000145:classification / Q000175:diagnosis* / Q000473:pathology; D010743:Phospholipids / Q000097:blood*; D012680:Sensitivity and Specificity; D060388:Support Vector Machine
D014408:Biomarkers, Tumor; D018394:CA-125 Antigen; D010743:Phospholipids