Skip to main content
Top
Published in: Medical Oncology 1/2015

01-01-2015 | Original Paper

High Jagged1 expression is associated with poor outcome in primary glioblastoma

Authors: Xian-xin Qiu, Chen-hong Wang, Na You, Bi-juan Chen, Xing-fu Wang, Yu-peng Chen, Zhi-xiong Lin

Published in: Medical Oncology | Issue 1/2015

Login to get access

Abstract

Glioblastoma is a highly aggressive brain tumor. Aberrant Notch pathway has been implicated in the formation and progression of glioblastoma. The present study attempted to investigate the expression of Notch ligand Jagged1 and its association with patient outcome in primary glioblastoma. Tumor tissues from 82 patients with primary glioblastoma were analyzed using immunohistochemistry for Jagged1 expression. Relationships between Jagged1 expression and clinical features (age, gender, KPS, symptom duration, extent of resection and Ki67 index) were evaluated. The prognostic value of Jagged1 was assessed using the Kaplan–Meier survival estimates and the Cox proportional hazard models. Immunohistochemistry results showed markedly increased Jagged1 expression in glioblastoma tissues compared to adjacent non-neoplastic brain tissues. Univariate analysis documented that high Jagged1 expression in tumor cells (TC) and endothelial cells (EC) were both statistically associated with reduced time to progression (TTP) (P < 0.001 for TC, P = 0.001 for EC) and overall survival (OS) (P < 0.001 for TC, P = 0.003 for EC) in primary glioblastoma. The median TTP (P < 0.001) and OS (P = 0.001) were higher in patients with dual-low Jagged1 expression in TC and EC compared to those in patients with non-dual Jagged1 expression and dual high expression. By multivariate survival analysis, we found that high Jagged1 expression in both tumor cells and endothelial cells was independent unfavorable prognostic factors TTP (P < 0.001 for TC, P < 0.001 for TC) and OS (P < 0.001 for TC, P < 0.001 for TC) in primary glioblastoma patients. Jagged1–Notch signaling plays an important role in the progress of glioblastoma. Jagged1 expression may be used as an independent prognosis factor in patients with glioblastoma.
Appendix
Available only for authorised users
Literature
3.
go back to reference Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005;352(10):987–96. doi:10.1056/NEJMoa043330.CrossRefPubMed Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005;352(10):987–96. doi:10.​1056/​NEJMoa043330.CrossRefPubMed
4.
go back to reference Artavanis-Tsakonas S, Rand MD, Lake RJ. Notch signaling: cell fate control and signal integration in development. Science. 1999;284(5415):770–6.CrossRefPubMed Artavanis-Tsakonas S, Rand MD, Lake RJ. Notch signaling: cell fate control and signal integration in development. Science. 1999;284(5415):770–6.CrossRefPubMed
6.
go back to reference Allenspach EJ, Maillard I, Aster JC, Pear WS. Notch signaling in cancer. Cancer Biol Ther. 2002;1(5):466–76.CrossRefPubMed Allenspach EJ, Maillard I, Aster JC, Pear WS. Notch signaling in cancer. Cancer Biol Ther. 2002;1(5):466–76.CrossRefPubMed
11.
go back to reference Reedijk M, Odorcic S, Chang L, Zhang H, Miller N, McCready DR, et al. High-level coexpression of JAG1 and NOTCH1 is observed in human breast cancer and is associated with poor overall survival. Cancer Res. 2005;65(18):8530–7. doi:10.1158/0008-5472.CAN-05-1069.CrossRefPubMed Reedijk M, Odorcic S, Chang L, Zhang H, Miller N, McCready DR, et al. High-level coexpression of JAG1 and NOTCH1 is observed in human breast cancer and is associated with poor overall survival. Cancer Res. 2005;65(18):8530–7. doi:10.​1158/​0008-5472.​CAN-05-1069.CrossRefPubMed
13.
15.
go back to reference Yu Y, Khan J, Khanna C, Helman L, Meltzer PS, Merlino G. Expression profiling identifies the cytoskeletal organizer ezrin and the developmental homeoprotein Six-1 as key metastatic regulators. Nat Med. 2004;10(2):175–81. doi:10.1038/nm966.CrossRefPubMed Yu Y, Khan J, Khanna C, Helman L, Meltzer PS, Merlino G. Expression profiling identifies the cytoskeletal organizer ezrin and the developmental homeoprotein Six-1 as key metastatic regulators. Nat Med. 2004;10(2):175–81. doi:10.​1038/​nm966.CrossRefPubMed
18.
go back to reference Barker FG II, Chang SM, Larson DA, Sneed PK, Wara WM, Wilson CB et al. Age and radiation response in glioblastoma multiforme. Neurosurgery. 2001;49(6):1288–97; discussion 97–8. Barker FG II, Chang SM, Larson DA, Sneed PK, Wara WM, Wilson CB et al. Age and radiation response in glioblastoma multiforme. Neurosurgery. 2001;49(6):1288–97; discussion 97–8.
19.
20.
go back to reference Wen PY, Macdonald DR, Reardon DA, Cloughesy TF, Sorensen AG, Galanis E, et al. Updated response assessment criteria for high-grade gliomas: response assessment in neuro-oncology working group. J Clin Oncol. 2010;28(11):1963–72. doi:10.1200/JCO.2009.26.3541.CrossRefPubMed Wen PY, Macdonald DR, Reardon DA, Cloughesy TF, Sorensen AG, Galanis E, et al. Updated response assessment criteria for high-grade gliomas: response assessment in neuro-oncology working group. J Clin Oncol. 2010;28(11):1963–72. doi:10.​1200/​JCO.​2009.​26.​3541.CrossRefPubMed
21.
go back to reference Sanghera P, Perry J, Sahgal A, Symons S, Aviv R, Morrison M, et al. Pseudoprogression following chemoradiotherapy for glioblastoma multiforme. Can J Neurol Sci. 2010;37(1):36–42.CrossRefPubMed Sanghera P, Perry J, Sahgal A, Symons S, Aviv R, Morrison M, et al. Pseudoprogression following chemoradiotherapy for glioblastoma multiforme. Can J Neurol Sci. 2010;37(1):36–42.CrossRefPubMed
22.
go back to reference Massi D, Tarantini F, Franchi A, Paglierani M, Di Serio C, Pellerito S, et al. Evidence for differential expression of Notch receptors and their ligands in melanocytic nevi and cutaneous malignant melanoma. Mod Pathol. 2006;19(2):246–54. doi:10.1038/modpathol.3800526.CrossRefPubMed Massi D, Tarantini F, Franchi A, Paglierani M, Di Serio C, Pellerito S, et al. Evidence for differential expression of Notch receptors and their ligands in melanocytic nevi and cutaneous malignant melanoma. Mod Pathol. 2006;19(2):246–54. doi:10.​1038/​modpathol.​3800526.CrossRefPubMed
25.
go back to reference Arndt S, Turvey C, Andreasen NC. Correlating and predicting psychiatric symptom ratings: Spearman's r versus Kendall's tau correlation. J Psychiat Res. 1999;33(2):97–104. Arndt S, Turvey C, Andreasen NC. Correlating and predicting psychiatric symptom ratings: Spearman's r versus Kendall's tau correlation. J Psychiat Res. 1999;33(2):97–104.
26.
31.
go back to reference Jansen MH, Veldhuijzen van Zanten SE, Sanchez Aliaga E, Heymans MW, Warmuth-Metz M, Hargrave D et al. Survival prediction model of children with diffuse intrinsic pontine glioma based on clinical and radiological criteria. Neuro-oncology. 2014. doi:10.1093/neuonc/nou104. Jansen MH, Veldhuijzen van Zanten SE, Sanchez Aliaga E, Heymans MW, Warmuth-Metz M, Hargrave D et al. Survival prediction model of children with diffuse intrinsic pontine glioma based on clinical and radiological criteria. Neuro-oncology. 2014. doi:10.​1093/​neuonc/​nou104.
32.
go back to reference LaVoie MJ, Selkoe DJ. The Notch ligands, Jagged and Delta, are sequentially processed by alpha-secretase and presenilin/gamma-secretase and release signaling fragments. J Biol Chem. 2003;278(36):34427–37. doi:10.1074/jbc.M302659200.CrossRefPubMed LaVoie MJ, Selkoe DJ. The Notch ligands, Jagged and Delta, are sequentially processed by alpha-secretase and presenilin/gamma-secretase and release signaling fragments. J Biol Chem. 2003;278(36):34427–37. doi:10.​1074/​jbc.​M302659200.CrossRefPubMed
33.
go back to reference John GR, Shankar SL, Shafit-Zagardo B, Massimi A, Lee SC, Raine CS, et al. Multiple sclerosis: re-expression of a developmental pathway that restricts oligodendrocyte maturation. Nat Med. 2002;8(10):1115–21. doi:10.1038/nm781.CrossRefPubMed John GR, Shankar SL, Shafit-Zagardo B, Massimi A, Lee SC, Raine CS, et al. Multiple sclerosis: re-expression of a developmental pathway that restricts oligodendrocyte maturation. Nat Med. 2002;8(10):1115–21. doi:10.​1038/​nm781.CrossRefPubMed
34.
go back to reference Khanna C, Wan X, Bose S, Cassaday R, Olomu O, Mendoza A, et al. The membrane-cytoskeleton linker ezrin is necessary for osteosarcoma metastasis. Nat Med. 2004;10(2):182–6. doi:10.1038/nm982.CrossRefPubMed Khanna C, Wan X, Bose S, Cassaday R, Olomu O, Mendoza A, et al. The membrane-cytoskeleton linker ezrin is necessary for osteosarcoma metastasis. Nat Med. 2004;10(2):182–6. doi:10.​1038/​nm982.CrossRefPubMed
38.
go back to reference Bao S, Wu Q, McLendon RE, Hao Y, Shi Q, Hjelmeland AB, et al. Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature. 2006;444(7120):756–60. doi:10.1038/nature05236.CrossRefPubMed Bao S, Wu Q, McLendon RE, Hao Y, Shi Q, Hjelmeland AB, et al. Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature. 2006;444(7120):756–60. doi:10.​1038/​nature05236.CrossRefPubMed
Metadata
Title
High Jagged1 expression is associated with poor outcome in primary glioblastoma
Authors
Xian-xin Qiu
Chen-hong Wang
Na You
Bi-juan Chen
Xing-fu Wang
Yu-peng Chen
Zhi-xiong Lin
Publication date
01-01-2015
Publisher
Springer US
Published in
Medical Oncology / Issue 1/2015
Print ISSN: 1357-0560
Electronic ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-014-0341-9

Other articles of this Issue 1/2015

Medical Oncology 1/2015 Go to the issue