Of
all of the epithelial ovarian cancers (EOC), clear cell adenocarcinoma
(CCA) has the worst clinical prognosis. Furthermore, the conventional
EOC biomarker CA125 is more often negative in CCA than in other subtypes
of EOC. This study sought to discover a new diagnostic biomarker that
would allow more reliable detection of CCA. Using mass spectrometry,
we compared proteins in conditioned media from cell lines derived
from CCA and other types of EOC. We identified 30 extracellular or
released proteins specifically present in CCA-derived cell lines.
Bioinformatics analyses identified a serine protease inhibitor, tissue
factor pathway inhibitor 2 (TFPI2), as a potential biomarker for CCA.
Real time RT-PCR and Western blot analyses revealed that TFPI2 was
exclusively expressed in CCA-derived cell lines and tissues. For clinical
validation, we measured levels of TFPI2 and CA125 in a set of sera
from 30 healthy women, 30 patients with endometriosis, and 50 patients
with CCA, using an automated enzyme-linked immunosorbent assay systems.
Serum levels of TFPI2 were significantly elevated in CCA patients,
even those with normal CA125 levels. In terms of area under the receiver
operating characteristic curve (AUC), TFPI2 was superior to CA125
in discriminating CCA patients from healthy women (AUC 0.97 for TFPI2
versus AUC 0.80 for CA125), or from patients with endometriosis (AUC
0.93 for TFPI2 versus 0.80 for CA125). This is the first evidence
for TFPI2 as a serum biomarker of CCA. We propose that this biomarker
may be useful for detection of CCA and for monitoring the transformation
from endometriosis into CCA
