Ovarian cancer (OVC) remains the most lethal gynecological
malignancy in the world due to the combined lack of early-stage diagnostics and effective therapeutic strategies. The development and application of advanced proteomics technology and new experimental models has created unique opportunities for translational studies. In this study, we investigated the
ovarian cancer proteome of the chicken, an emerging experimental model of OVC that develops ovarian
tumors spontaneously. Matched plasma, ovary, and oviduct tissue biospecimens derived from healthy, early-stage OVC, and late-stage OVC birds were quantitatively characterized by label-free proteomics. Over 2600
proteins were identified in this study, 348 of which were differentially expressed by more than twofold (p ≤ 0.05) in early- and late-stage ovarian
tumor tissue specimens relative to healthy ovarian tissues. Several of the 348
proteins are known to be differentially regulated in human
cancers including B2M, CLDN3,
EPCAM, PIGR, S100A6, S100A9, S100A11, and TPD52. Of particular interest was
ovostatin 2 (OVOS2), a novel 165-kDa
protease inhibitor found to be strongly upregulated in chicken ovarian
tumors (p = 0.0005) and matched plasma (p = 0.003). Indeed, RT-quantitative PCR and Western blot analysis demonstrated that OVOS2
mRNA and
protein were also upregulated in multiple human OVC cell lines compared to normal ovarian epithelia (NOE) cells and immunohistochemical staining confirmed overexpression of OVOS2 in primary human
ovarian cancers relative to non-cancerous tissues. Collectively, these data provide the first evidence for involvement of OVOS2 in the pathogenesis of both chicken and human
ovarian cancer.