title: Cathepsin D is a potential serum marker for poor prognosis in glioma patients.
abstract: Cathepsin D is an aspartyl protease involved in protein catabolism and tissue remodeling which can be secreted from cancer cells. To identify a potential serum marker for gliomas, we investigated the gene expression levels of cathepsin D in 87 tissue samples and measured the protein concentrations in sera of glioma patients. The tissue samples consisted of 43 glioblastomas, 13 anaplastic astrocytomas, 22 astrocytomas, and 9 normal brain tissues. The results of real-time quantitative reverse transcription-PCR analysis showed that cathepsin D transcript levels became significantly higher as the glioma grade advanced (P = 0.0466, glioblastoma and anaplastic astrocytoma; P = 0.0008, glioblastoma and astrocytoma; P = 0.0271, glioblastoma and normal brain tissue; unpaired t test). Immunohistochemical analysis with anti-cathepsin D antibody revealed dense and spotty staining in the tumor cells with high transcript levels. The low expression of cathepsin D significantly correlated with long survival of the glioma patients. Furthermore, the glioblastoma patients with high gene expression of cathepsin D lived significantly shorter than those with low expression (P = 0.0104, Cox-Mantel log-rank test) and frequently had leptomeningeal dissemination (P = 0.0016, chi2 test). The multivariate analysis confirmed that the cathepsin D expression level was an independent predictor for short survival (P = 0.0102, Cox proportional hazard regression model). Measurement of the serum cathepsin D concentrations by ELISA showed a significant increase in the patients with high-grade gliomas as compared with the low-grade tumors (P = 0.0081, chi2 test). These results collectively suggest that cathepsin D could be a potential serum marker for the prediction of aggressive nature of human gliomas.
authors.affiliation: Department of Neurological Surgery, Chiba University Graduate School of Medicine, Chiba, Japan.
authors.forename: Mieko E
authors.initials: ME
authors.lastname: Fukuda
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Iwadate
authors.forename: Toshio
authors.initials: T
authors.lastname: Machida
authors.forename: Takaki
authors.initials: T
authors.lastname: Hiwasa
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Nimura
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Nagai
authors.forename: Masaki
authors.initials: M
authors.lastname: Takiguchi
authors.forename: Hideki
authors.initials: H
authors.lastname: Tanzawa
authors.forename: Akira
authors.initials: A
authors.lastname: Yamaura
authors.forename: Naohiko
authors.initials: N
authors.lastname: Seki
mesh_terms: D001254:Astrocytoma / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000097:blood* / Q000235:genetics; D001932:Brain Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D002402:Cathepsin D / Q000096:biosynthesis / Q000097:blood* / Q000235:genetics; D015870:Gene Expression; D005909:Glioblastoma / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008577:Meningeal Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D011379:Prognosis
chemical_list: D014408:Biomarkers, Tumor; D002402:Cathepsin D