Osteopontin as a Potential Diagnostic Biomarker for Ovarian Cancer
Jae Hoon Kim,Steven J. Skates,Toshimitsu Uede,Kwong Kwok Wong,John O. Schorge,Colleen M. Feltmate,Ross S. Berkowitz,Daniel W. Cramer,Samuel C. Mok +8 more
TLDR
The findings provide evidence for an association between levels of a biomarker, osteopontin, and ovarian cancer and suggest that future research assessing its clinical usefulness would be worthwhile.Abstract:
ContextDevelopment of new biomarkers for ovarian cancer is needed for early
detection and disease monitoring. Analyses involving complementary DNA (cDNA)
microarray data can be used to identify up-regulated genes in cancer cells,
whose products may then be further validated as potential biomarkers.ObjectiveTo describe validation studies of an up-regulated gene known as osteopontin,
previously identified using a cDNA microarray system.Design, Setting, and ParticipantsExperimental and cross-sectional studies were conducted involving ovarian
cancer and healthy human ovarian surface epithelial cell lines and cultures,
archival paraffin-embedded ovarian tissue collected between June 1992 and
June 2001, and fresh tissue and preoperative plasma from 144 patients evaluated
for a pelvic mass between June 1992 and June 2001 in gynecologic oncology
services at 2 US academic institutions. Plasma samples from 107 women selected
from an epidemiologic study of ovarian cancer initiated between May 1992 and
March 1997 were used as healthy controls.Main Outcome MeasuresRelative messenger RNA expression in cancer cells and fresh ovarian
tissue, measured by real-time polymerase chain reaction as 2−ΔΔCT(a quantitative value representing the amount of osteopontin expression);
osteopontin production, localized and scored in ovarian healthy and tumor
tissue with immunohistochemical studies; and amount of osteopontin in patient
vs control plasma, measured using an enzyme-linked immunoassay.ResultsThe geometric mean for 2−ΔΔCTfor osteopontin
expression in 5 healthy ovarian epithelial cell cultures was 4.1 compared
with 270.4 in 14 ovarian cancer cell lines (P = .03).
The geometric mean 2−ΔΔCTfor osteopontin expression
in tissue from 2 healthy ovarian epithelial samples was 9.0 compared with
164.0 in 27 microdissected ovarian tumor tissue samples (P = .06). Immunolocalization of osteopontin showed that tissue samples
from 61 patients with invasive ovarian cancer and 29 patients with borderline
ovarian tumors expressed higher levels of osteopontin than tissue samples
from 6 patients with benign tumors and samples of healthy ovarian epithelium
from 3 patients (P = .03). Osteopontin levels in
plasma were significantly higher (P<.001) in 51
patients with epithelial ovarian cancer (486.5 ng/mL) compared with those
of 107 healthy controls (147.1 ng/mL), 46 patients with benign ovarian disease
(254.4 ng/mL), and 47 patients with other gynecologic cancers (260.9 ng/mL).ConclusionsOur findings provide evidence for an association between levels of a
biomarker, osteopontin, and ovarian cancer and suggest that future research
assessing its clinical usefulness would be worthwhile.read more
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