The serine protease prostasin (PRSS8) is a potential biomarker for early detection of ovarian cancer

Abstract

BackgroundOvarian cancer (OVC) is the deadliest of all gynecologic cancers, primarily as a consequence of asymptomatic progression. The complex nature of OVC creates challenges for early detection, and there is a lack of specific and sensitive biomarkers suitable for screening and detecting early stage OVC.MethodsPotential OVC biomarkers were identified by bioinformatic analysis. Candidates were further screened for differential expression in a library of OVC cell lines. OVC-specific overexpression of a candidate gene, PRSS8, which encodes prostasin, was confirmed against 18 major human cancer types from 390 cancer samples by qRT-PCR. PRSS8 expression profiles stratified by OVC tumor stage-, grade- and subtype were generated using cDNA samples from 159 OVC samples. Cell-specific expression and localization of prostasin was determined by immunohistological tissue array analysis of more than 500 normal, benign, and cancerous ovarian tissues. The presence of prostasin in normal, benign, and OVC serum samples was also determined.ResultsGene expression analysis indicated that PRSS8 was expressed in OVC at levels more than 100 fold greater than found in normal or benign ovarian lesions. This overexpression signature was found in early stages of OVC and was maintained in higher stages and grades of OVC. The PRSS8 overexpression signature was specific for OVC and urinary bladder cancer among 18 human cancer types. The majority of ovarian cell lines overexpressed PRSS8. In situ hybridization and histopathology studies of OVC tissues indicated that overexpression of prostasin was largely localized to tumor epithelium and was absent in neighboring stroma. Significantly higher levels of prostasin were found in early stage OVC serum samples compared to benign ovarian and normal donor samples.ConclusionsThe abundant amounts of secreted prostasin found in sera of early stage OVC can potentially be used as a minimally invasive screening biomarker for early stage OVC. Overexpression of PRSS8 mRNA and high levels of prostasin in multiple subtypes of early stage ovarian tumors may provide clinical biomarkers for early detection of OVC, which can potentially be used with CA125 and HE4.Electronic supplementary materialThe online version of this article (doi:10.1186/s13048-016-0228-9) contains supplementary material, which is available to authorized users.

A two-step strategy for identification of plasma protein biomarkers for endometrial and ovarian cancer

“…Among the proteins we identified as biomarker candidates for OC some have been discussed previously [ 5 ], such as Mucin-16 (CA125) and Major epididymis-specific protein E4 (HE4), Midkine (MK) [ 16 , 17 ], Kallikrein-11 (hK11) [ 18 ], Folate receptor alpha (FR) [ 19 , 20 ] and Prostasin (PRSS8) [ 21 , 22 ]. Boylan et al [ 5 ] also using PEA technology further reported an association of OC with Interleukin-6 (IL-6) [ 23 – 25 ], Kallikrein-6 (KLK6) [ 26 ], Furin (FUR) [ 27 ], Chemokine (C-X-C motif) ligand 13 (CXCL13) and Tumor necrosis factor ligand superfamily member 14 (TNFSF14), but none of these proteins were among our top candidates.…”

A multiplex platform for the identification of ovarian cancer biomarkers

“…Mok et al [ 64 ] demonstrated an upregulation of human prostasin (PRSS8) in ovarian cancer cells compared to normal cells, and increased levels of PRSS8 in sera from ovarian cancer patients compared to normal controls. Recent western blot analysis of sera that had been depleted of the highly abundant proteins showed that PRSS8 levels were increased in early stage ovarian cancer samples compared to benign samples or healthy controls [ 65 ]. Our Proseek ® data corroborated these results as we found that PRSS8 is noticeably higher in the sera of women with early and late stage ovarian cancer as compared to healthy women or women with benign ovarian disease.…”

Membrane-Anchored Serine Proteases and Protease-Activated Receptor-2–Mediated Signaling: Co-Conspirators in Cancer Progression

“…Hepsin, prostasin, and TMPRSS2 upregulation in epithelial breast, prostate, and ovarian cancer cell lines, mouse models, and patient samples are believed to contribute to increased proliferation, tumor growth, metastasis, ascites formation, and various other invasive processes (107,(113)(114)(115)(116)(117)(118)(119)(120)(121)(122)(123)(124)(125). Overexpression of hepsin in prostate epithelium in a prostate tumor model (LPB-Tag mice) resulted in increased basement membrane disorganization and tumor metastasis to distant organs, which did not occur in control mice, indicating that hepsin is capable of promoting prostate cancer metastatic processes (119).…”