A multiparametric panel for ovarian cancer diagnosis, prognosis, and response to chemotherapy.
OBJECTIVE
Our goal was to examine a panel of 11 biochemical variables, measured in cytosolic extracts of ovarian tissues (normal, benign, and malignant) by quantitative ELISAs for their ability to diagnose, prognose, and predict response to chemotherapy of ovarian cancer patients.


METHODS
Eleven proteins were measured (9 kallikreins, B7-H4, and CA125) in cytosolic extracts of 259 ovarian tumor tissues, 50 tissues from benign conditions, 35 normal tissues, and 44 tissues from nonovarian tumors that metastasized to the ovary. Odds ratios and hazard ratios and their 95% confidence interval were calculated. Time-dependent receiver operating characteristic curves for censored survival data were used to evaluate the performance of the biomarkers. Resampling was used to validate the performance.


RESULTS
Most biomarkers effectively separated cancer from noncancer groups. A composite marker provided an area under the curve of 0.97 (95% confidence interval, 0.95-0.99) for discriminating normal and cancer groups. Univariately, hK5 and hK6 were positively associated with progression. After adjusting for clinical variables in multivariate analysis, both hK10 and hK11 significantly predicted time to progression. Increasing levels of hK13 were associated with chemotherapy response, and the predictive power of hK13 to chemotherapy response was improved by a panel of five biomarkers.


CONCLUSIONS
The evidence shows that a group of kallikreins and multiparametric combinations with other biomarkers and clinical variables can significantly assist with ovarian cancer classification, prognosis, and response to platinum-based chemotherapy. In particular, we developed a multiparametric strategy for predicting ovarian cancer response to chemotherapy, comprising several biomarkers and clinical features.
The Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
Yingye
Y
Zheng
Dionyssios
D
Katsaros
Shannon J C
SJ
Shan
Irene Rigault
IR
de la Longrais
Mauro
M
Porpiglia
Andreas
A
Scorilas
Nam W
NW
Kim
Robert L
RL
Wolfert
Iris
I
Simon
Lin
L
Li
Ziding
Z
Feng
Eleftherios P
EP
Diamandis
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018122:B7-1 Antigen / Q000032:analysis; D014408:Biomarkers, Tumor / Q000032:analysis*; D018394:CA-125 Antigen / Q000032:analysis; D003600:Cytosol / Q000378:metabolism; D018572:Disease-Free Survival; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006801:Humans; D007610:Kallikreins / Q000032:analysis / Q000097:blood; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000175:diagnosis* / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011379:Prognosis; D060907:V-Set Domain-Containing T-Cell Activation Inhibitor 1
D018122:B7-1 Antigen; D014408:Biomarkers, Tumor; D018394:CA-125 Antigen; D060907:V-Set Domain-Containing T-Cell Activation Inhibitor 1; C475826:VTCN1 protein, human; D007610:Kallikreins