Cathepsin D Is a Potential Serum Marker for Poor Prognosis in Glioma Patients

• DOI: 10.1158/0008-5472.can-04-4134
• Publication Date: 2005-09-15T21:53:09Z
• Authors: Mieko E. Fukuda; Yasuo Iwadate; Toshio Machida; Takaki Hiwasa; Yoshinori Nimura; Yuichiro Nagai; Masaki Takiguchi; Hideki Tanzawa; Akira Yamaura; Naohiko Seki
• Keywords: Brain Neoplasms; Gene Expression; Astrocytoma; Prognosis; Cathepsin D; Immunohistochemistry; 3. Good health; 03 medical and health sciences; 0302 clinical medicine; Biomarkers, Tumor; Meningeal Neoplasms; Humans; Glioblastoma

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, χ2 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, χ2 test). These results collectively suggest that cathepsin D could be a potential serum marker for the prediction of aggressive nature of human gliomas.