Skip to main content
Top
Published in: Medical Oncology 4/2012

01-12-2012 | Original Paper

Progranulin overexpression predicts overall survival in patients with glioblastoma

Authors: Minqing Wang, Gang Li, Junyi Yin, Tao Lin, Jian Zhang

Published in: Medical Oncology | Issue 4/2012

Login to get access

Abstract

Despite multimodal treatment, patients with astrocytoma still face a poor survival, and identification of valuable prognostic factors is crucial to yield effective individual therapy strategies. The aim of this study was to investigate progranulin (PGRN) expression in astrocytomas and explore its association with tumor grade and overall patient survival by scoring the PGRN immunoreactivity of both tumor cells and blood vessels. About 210 astrocytoma samples with different WHO grades and 14 normal brain tissues were studied by immunohistochemistry for PGRN. Semi-quantitative RT-PCR and Western blot were carried out to confirm its expression in 35 tumor specimens. Serum levels of PGRN in glioblastoma were examined by enzyme immunometric assay. PGRN expression was almost undetectable in the normal brain tissues by immunohistochemistry but increased in both astrocytoma cells and tumor blood vessels with pathological grading. Sera in glioblastoma were significantly higher than in healthy control. In grade II astrocytoma, strong vascular PGRN expression was closely related to tumor recurrence. In glioblastoma, high total PGRN expression, strong vascular PGRN expression, and strong tumor cellular PGRN expression all correlated with decreased patient survival in univariate analysis. However, only total PGRN expression as well as vascular PGRN expression status was independently associated with patient’s survival in the multivariate analysis. These results suggest that PGRN, involved in astrocytoma progression, may serve as a prognostic biomarker for glioblastoma.
Literature
1.
go back to reference Liu Q, Li G, Li R, Shen J, et al. IL-6 promotion of glioblastoma cell invasion and angiogenesis in U251 and T98G cell lines. J Neurooncol. 2010;100:165–76.PubMedCrossRef Liu Q, Li G, Li R, Shen J, et al. IL-6 promotion of glioblastoma cell invasion and angiogenesis in U251 and T98G cell lines. J Neurooncol. 2010;100:165–76.PubMedCrossRef
2.
go back to reference Arrieta O, Garcia E, Guevara P, et al. Hepatocyte growth factor is associated with poor prognosis of malignant gliomas and is a predictor for recurrence of meningioma. Cancer. 2002;94:3210–8.PubMedCrossRef Arrieta O, Garcia E, Guevara P, et al. Hepatocyte growth factor is associated with poor prognosis of malignant gliomas and is a predictor for recurrence of meningioma. Cancer. 2002;94:3210–8.PubMedCrossRef
3.
go back to reference He Z, Bateman A. Progranulin (granulin–epithelin precursor, PC-cell-derived growth factor, acrogranin) mediates tissue repair and tumorigenesis. J Mol Med. 2003;81:600–12.PubMedCrossRef He Z, Bateman A. Progranulin (granulin–epithelin precursor, PC-cell-derived growth factor, acrogranin) mediates tissue repair and tumorigenesis. J Mol Med. 2003;81:600–12.PubMedCrossRef
4.
go back to reference Tangkeangsirisin W, Serrero G. PC cell-derived growth factor (PCDGF/GP88, progranulin) stimulates migration, invasiveness and VEGF expression in breast cancer cells. Carcinogenesis. 2004;25:1587–92.PubMedCrossRef Tangkeangsirisin W, Serrero G. PC cell-derived growth factor (PCDGF/GP88, progranulin) stimulates migration, invasiveness and VEGF expression in breast cancer cells. Carcinogenesis. 2004;25:1587–92.PubMedCrossRef
5.
go back to reference He Z, Ismail A, Kriazhev L, et al. Progranulin (PC-cell-derived growth factor/acrogranin) regulates invasion and cell survival. Cancer Res. 2002;62:5590–6.PubMed He Z, Ismail A, Kriazhev L, et al. Progranulin (PC-cell-derived growth factor/acrogranin) regulates invasion and cell survival. Cancer Res. 2002;62:5590–6.PubMed
6.
go back to reference Liu Y, Xi L, Liao G, et al. Inhibition of PC cell-derived growth factor (PCDGF)/granulin–epithelin precursor (GEP) decreased cell proliferation and invasion through downregulation of cyclin D and CDK4 and inactivation of MMP-2. BMC Cancer. 2007;7:22.PubMedCrossRef Liu Y, Xi L, Liao G, et al. Inhibition of PC cell-derived growth factor (PCDGF)/granulin–epithelin precursor (GEP) decreased cell proliferation and invasion through downregulation of cyclin D and CDK4 and inactivation of MMP-2. BMC Cancer. 2007;7:22.PubMedCrossRef
7.
go back to reference Kamrava M, Simpkins F, Alejandro E, et al. Lysophosphatidic acid and endothelin-induced proliferation of ovarian cancer cell lines is mitigated by neutralization of granulin-epithelin precursor (GEP), a prosurvival factor for ovarian cancer. Oncogene. 2005;24:7084–93.PubMedCrossRef Kamrava M, Simpkins F, Alejandro E, et al. Lysophosphatidic acid and endothelin-induced proliferation of ovarian cancer cell lines is mitigated by neutralization of granulin-epithelin precursor (GEP), a prosurvival factor for ovarian cancer. Oncogene. 2005;24:7084–93.PubMedCrossRef
8.
go back to reference Monami G, Emiliozzi V, Bitto A, et al. Proepithelin regulates prostate cancer cell biology by promoting cell growth, migration, and anchorage-independent growth. Am J Pathol. 2009;174:1037–47.PubMedCrossRef Monami G, Emiliozzi V, Bitto A, et al. Proepithelin regulates prostate cancer cell biology by promoting cell growth, migration, and anchorage-independent growth. Am J Pathol. 2009;174:1037–47.PubMedCrossRef
9.
go back to reference Liau LM, Lallone RL, Seitz RS, et al. Identification of a human glioma-associated growth factor gene, granulin, using differential immuno-absorption. Cancer Res. 2000;60:1353–60.PubMed Liau LM, Lallone RL, Seitz RS, et al. Identification of a human glioma-associated growth factor gene, granulin, using differential immuno-absorption. Cancer Res. 2000;60:1353–60.PubMed
10.
go back to reference Cheung ST, Wong SY, Leung KL, et al. Granulin-epithelin precursor over-expression promotes growth and invasion of hepatocellular carcinoma. Clin Cancer Res. 2004;10:7629–36.PubMedCrossRef Cheung ST, Wong SY, Leung KL, et al. Granulin-epithelin precursor over-expression promotes growth and invasion of hepatocellular carcinoma. Clin Cancer Res. 2004;10:7629–36.PubMedCrossRef
11.
go back to reference Pan CX, Kinch MS, Kiener PA, et al. PC cell-derived growth factor expression in prostatic intraepithelial neoplasia and prostatic adenocarcinoma. Clin Cancer Res. 2004;10:1333–7.PubMedCrossRef Pan CX, Kinch MS, Kiener PA, et al. PC cell-derived growth factor expression in prostatic intraepithelial neoplasia and prostatic adenocarcinoma. Clin Cancer Res. 2004;10:1333–7.PubMedCrossRef
12.
go back to reference Davidson B, Alejandro E, Florenes VA, et al. Granulin-epithelin precursor is a novel prognostic marker in epithelial ovarian carcinoma. Cancer. 2004;100:2139–47.PubMedCrossRef Davidson B, Alejandro E, Florenes VA, et al. Granulin-epithelin precursor is a novel prognostic marker in epithelial ovarian carcinoma. Cancer. 2004;100:2139–47.PubMedCrossRef
13.
go back to reference Serrero G, Ioffe OB. Expression of PC-cell-derived growth factor in benign and malignant human breast epithelium. Hum Pathol. 2003;34:1148–54.PubMedCrossRef Serrero G, Ioffe OB. Expression of PC-cell-derived growth factor in benign and malignant human breast epithelium. Hum Pathol. 2003;34:1148–54.PubMedCrossRef
14.
go back to reference Cheung ST, Cheung PF, Cheng CK, et al. Granulin-epithelin precursor and ATP-dependent binding cassette (ABC) B5 regulate liver cancer cell chemoresistance. Gastroenterology. 2011;140:344–55.PubMedCrossRef Cheung ST, Cheung PF, Cheng CK, et al. Granulin-epithelin precursor and ATP-dependent binding cassette (ABC) B5 regulate liver cancer cell chemoresistance. Gastroenterology. 2011;140:344–55.PubMedCrossRef
15.
go back to reference Kim WE and Serrero G. PC cell-derived growth factor stimulates proliferation and confers Trastuzumab resistance to Her-2-overexpressing breast cancer cells. Clin Cancer Res. 2006;12:4192–9.CrossRef Kim WE and Serrero G. PC cell-derived growth factor stimulates proliferation and confers Trastuzumab resistance to Her-2-overexpressing breast cancer cells. Clin Cancer Res. 2006;12:4192–9.CrossRef
16.
go back to reference Ho JC, Ip YC, Cheung ST, et al. Granulin-epithelin precursor as a therapeutic target for hepatocellular carcinoma. Hepatology. 2008;47:1524–32.PubMedCrossRef Ho JC, Ip YC, Cheung ST, et al. Granulin-epithelin precursor as a therapeutic target for hepatocellular carcinoma. Hepatology. 2008;47:1524–32.PubMedCrossRef
17.
go back to reference Elkabets M, Gifford AM, Scheel C, Nilsson B, et al. Human tumors instigate granulin-expressing hematopoietic cells that promote malignancy by activating stromal fibroblasts in mice. J Clin Invest. 2011;121:784–99.PubMedCrossRef Elkabets M, Gifford AM, Scheel C, Nilsson B, et al. Human tumors instigate granulin-expressing hematopoietic cells that promote malignancy by activating stromal fibroblasts in mice. J Clin Invest. 2011;121:784–99.PubMedCrossRef
18.
go back to reference Chen XY, Li JS, Liang QP, et al. Expression of PC cell-derived growth factor and vascular endothelial growth factor in esophageal squamous cell carcinoma and their clinicopathologic significance. Chin Med J (Engl). 2008;121:881–6. Chen XY, Li JS, Liang QP, et al. Expression of PC cell-derived growth factor and vascular endothelial growth factor in esophageal squamous cell carcinoma and their clinicopathologic significance. Chin Med J (Engl). 2008;121:881–6.
19.
go back to reference Tkaczuk KR, Yue B, Zhan M, et al. Increased circulating level of the survival factor gp88 (progranulin) in the serum of breast cancer patients when compared to healthy subjects. Breast Cancer (Auckl). 2011;5:155–62. Tkaczuk KR, Yue B, Zhan M, et al. Increased circulating level of the survival factor gp88 (progranulin) in the serum of breast cancer patients when compared to healthy subjects. Breast Cancer (Auckl). 2011;5:155–62.
20.
go back to reference Dhermain F, Saliou G, Parker F, et al. Microvascular leakage and contrast enhancement as prognostic factors for recurrence in unfavorable low-grade gliomas. J Neurooncol. 2010;97:81–8.PubMedCrossRef Dhermain F, Saliou G, Parker F, et al. Microvascular leakage and contrast enhancement as prognostic factors for recurrence in unfavorable low-grade gliomas. J Neurooncol. 2010;97:81–8.PubMedCrossRef
Metadata
Title
Progranulin overexpression predicts overall survival in patients with glioblastoma
Authors
Minqing Wang
Gang Li
Junyi Yin
Tao Lin
Jian Zhang
Publication date
01-12-2012
Publisher
Springer US
Published in
Medical Oncology / Issue 4/2012
Print ISSN: 1357-0560
Electronic ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-011-0131-6

Other articles of this Issue 4/2012

Medical Oncology 4/2012 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.