Secretome-Based Identification of TFPI2, A Novel Serum Biomarker for Detection of Ovarian Clear Cell Adenocarcinoma

Noriaki Arakawa, Etsuko Miyagi, Ayako Nomura, Erina Morita, Yoko Ino, Norihisa Ohtake, Yohei Miyagi, Fumiki Hirahara, Hisashi Hirano
Journal of proteome research · 2013 · vol. 12(10) , pp. 4340–4350 · doi:10.1021/pr400282j · PMID:23805888 · W2317820864
article OA: closed CC0 ⤵ 3 in-corpus citations
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This study identified tissue factor pathway inhibitor 2 (TFPI2) in conditioned media and serum as a novel biomarker superior to CA125 for detecting ovarian clear cell adenocarcinoma.

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Abstract

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.

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Condition tags

endometriosis

MeSH descriptors

Adenocarcinoma, Clear Cell Biomarkers, Tumor Glycoproteins Neoplasms, Glandular and Epithelial Ovarian Neoplasms Adenocarcinoma, Clear Cell Adenocarcinoma, Clear Cell Adult Aged Aged, 80 and over Biomarkers, Tumor Blood Proteins Blood Proteins Carcinoma, Ovarian Epithelial Case-Control Studies Cell Line, Tumor Female Glycoproteins Glycoproteins Humans

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