Sc. Mok et al., Prostasin, a potential serum marker for ovarian cancer: Identification through microarray technology, J NAT CANC, 93(19), 2001, pp. 1458-1464
Background: Screening biomarkers for ovarian cancer are needed because of i
ts late stage at diagnosis and poor survival. We used microarray technology
to identify overexpressed genes for secretory proteins as potential serum
biomarkers and selected prostasin, a serine protease normally secreted by t
he prostate gland, for further study. Methods: RNA was isolated and pooled
from three ovarian cancer cell lines and from three normal human ovarian su
rface epithelial (HOSE) cell lines. Complementary DNA generated from these
pools was hybridized to a microarray slide, and genes overexpressed in the
cancer cells were identified. Real-time quantitative polymerase chain react
ion was used to examine prostasin gene expression in ovarian cancer and HOS
E cell lines. Anti-prostasin antibodies were used to examine prostasin expr
ession and to measure serum prostasin by an enzyme-linked immunosorbent ass
ay in 64 case patients with ovarian cancer and in 137 control subjects. Pre
viously determined levels of CA 125, an ovarian cancer marker, were availab
le from about 70% of all subjects. All statistical tests were two-sided. Re
sults: Prostasin was detected by immunostaining more strongly in cancerous
ovarian epithelial cells and stroma than in normal ovarian tissue. The mean
level of serum prostasin was 13.7 mug/mL (95% confidence interval [CI] = 1
0.5 to 16.9 mug/mL) in 64 case patients with ovarian cancer and 7.5 mug/mL
(95% CI = 6.6 to 8.3 mug/mL) in 137 control subjects (P < .041, after adjus
tment for the subject's age, year of collection, and specimen quality). In
14 of 16 case patients with both preoperative and postoperative serum sampl
es, postoperative prostasin levels were statistically significantly lower t
han preoperative levels (P =.004). In 37 case patients with nonmucinous ova
rian cancer and in 100 control subjects for whom levels of CA 125 and prost
asin were available, the combination of markers gave a sensitivity of 92% (
95% CI = 78.1% to 98.3%) and a specificity of 94% (95% CI = 87.4% to 97.7%)
for detecting ovarian cancer. Conclusions: Prostasin is overexpressed in e
pithelial ovarian cancer and should be investigated further as a screening
or tumor marker, alone and in combination with CA 125.