Yasuko Yamamoto1, Naoe Goto2, Masao Takemura3, Wakana Yamasuge3, Kuniaki Yabe4, Tsuyoshi Takami5, Tatsuhiko Miyazaki6, Tamotsu Takeuchi7, Makoto Shiraki8, Masahito Shimizu8, Seiji Adachi2, Koshiro Saito2, Yuhei Shibata8, Nobuhiko Nakamura8, Takeshi Hara8, Ginette Serrero9, Kuniaki Saito1, Hisashi Tsurumi10. 1. Department of Disease Control and Prevention, Fujita Health University Graduate School of Health Sciences, Toyoake, Aichi, Japan; Human Health Sciences, Graduate School of Medicine, Faculty of Medicine, Kyoto University, Kyoto 606-8507, Japan. 2. Department of Hematology, Gihoku Kosei Hospital, Gifu, Japan. 3. Department of Disease Control and Prevention, Fujita Health University Graduate School of Health Sciences, Toyoake, Aichi, Japan. 4. R&D Division, A&T Corporation, Kanagawa, Japan. 5. The Tokai Cytopathology Institute Cancer Research and Prevention, Japan. 6. Pathology Division, Gifu University Hospital, Gifu, Japan. 7. Department of Pathology and Translational Research, Gifu University Graduate School of Medicine, Gifu, Japan. 8. First Department of Internal Medicine, Gifu University Graduate School of Medicine, Gifu, Japan. 9. R&D and Precision Antibody Divisions, A&G Pharmaceutical Inc., Columbia, MD, USA. 10. First Department of Internal Medicine, Gifu University Graduate School of Medicine, Gifu, Japan. Electronic address: htsuru@gifu-u.ac.jp.
Abstract
BACKGROUND: GP88 (progranulin; PGRN) is a secreted 88kDa glycosylated protein, with important functions, including inflammation and tumorigenesis. We assessed the significance of GP88 expression in survival outcomes of patients with malignant lymphoma (ML). METHODS: Serum samples from 254 previously untreated ML patients were examined to measure GP88 concentrations using a sandwich human GP88 ELISA kit. Immunohistochemical analyses were performed to examine GP88 tumor tissue expression. RESULTS: The median serum GP88 concentration of ML patients was 91.3ng/ml, and was significantly higher than that of the control group (median, 57.7ng/ml) (p<0.0001). Association between GP88 serum concentrations and overall survival (OS) was examined in patients with diffuse large B cell lymphoma (DLBCL) who had been stratified based on their serum GP88 concentrations. Kaplan Meier survival analysis showed that patients with serum GP88 concentrations of ≤116 and >116ng/ml, had 5-y OS rates of 70% and 50%, respectively (p=0.02). The immunohistochemical analyses of GP88 tumor expression revealed that DLBCL patients had lymphoma cells that were positive for GP88. CONCLUSIONS: High serum GP88 concentrations are associated with poor prognosis in patients with DLBCL.
BACKGROUND:GP88 (progranulin; PGRN) is a secreted 88kDa glycosylated protein, with important functions, including inflammation and tumorigenesis. We assessed the significance of GP88 expression in survival outcomes of patients with malignant lymphoma (ML). METHODS: Serum samples from 254 previously untreated MLpatients were examined to measure GP88 concentrations using a sandwich humanGP88 ELISA kit. Immunohistochemical analyses were performed to examine GP88tumor tissue expression. RESULTS: The median serum GP88 concentration of MLpatients was 91.3ng/ml, and was significantly higher than that of the control group (median, 57.7ng/ml) (p<0.0001). Association between GP88 serum concentrations and overall survival (OS) was examined in patients with diffuse large B cell lymphoma (DLBCL) who had been stratified based on their serum GP88 concentrations. Kaplan Meier survival analysis showed that patients with serum GP88 concentrations of ≤116 and >116ng/ml, had 5-y OS rates of 70% and 50%, respectively (p=0.02). The immunohistochemical analyses of GP88tumor expression revealed that DLBCL patients had lymphoma cells that were positive for GP88. CONCLUSIONS: High serum GP88 concentrations are associated with poor prognosis in patients with DLBCL.
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