The DOI matches its Crossref record; 7 of the 7 references it cites were found in a registry or an index.
Stem Cell–Related “Self-Renewal” Signature and High Epidermal Growth Factor Receptor Expression Associated With Resistance to Concomitant Chemoradiotherapy in Glioblastoma
Open accessAbstract
Purpose: Glioblastomas are notorious for resistance to therapy, which has been attributed to DNA-repair proficiency, a multitude of deregulated molecular pathways, and, more recently, to the particular biologic behavior of tumor stem-like cells. Here, we aimed to identify molecular profiles specific for treatment resistance to the current standard of care of concomitant chemoradiotherapy with the alkylating agent temozolomide. Patients and Methods: Gene expression profiles of 80 glioblastomas were interrogated for associations with resistance to therapy. Patients were treated within clinical trials testing the addition of concomitant and adjuvant temozolomide to radiotherapy. Results: An expression signature dominated by HOX genes, which comprises Prominin-1 (CD133), emerged as a predictor for poor survival in patients treated with concomitant chemoradiotherapy (n = 42; hazard ratio = 2.69; 95% CI, 1.38 to 5.26; P = .004). This association could be validated in an independent data set. Provocatively, the HOX cluster was reminiscent of a “self-renewal” signature (P = .008; Gene Set Enrichment Analysis) recently characterized in a mouse leukemia model. The HOX signature and EGFR expression were independent prognostic factors in multivariate analysis, adjusted for the O-6-methylguanine-DNA methyltransferase (MGMT) methylation status, a known predictive factor for benefit from temozolomide, and age. Better outcome was associated with gene clusters characterizing features of tumor-host interaction including tumor vascularization and cell adhesion, and innate immune response. Conclusion: This study provides first clinical evidence for the implication of a “glioma stem cell” or “self-renewal” phenotype in treatment resistance of glioblastoma. Biologic mechanisms identified here to be relevant for resistance will guide future targeted therapies and respective marker development for individualized treatment and patient selection.
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Cites
Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing
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Radiotherapy Plus Concomitant and Adjuvant Temozolomide for Glioblastoma
Stupp, R., Mason, W. P., van den Bent, M. J., Weller, M., Fisher, B., Taphoorn, M. J. B., Belanger, K., Brandes, A. A., Marosi, C., Bogdahn, U., et al. (2005) · New England Journal of Medicine · doi:10.1056/nejmoa043330 · Cited by 21,807
Self-citationMANTOVANI, A., SOZZANI, S., LOCATI, M., ALLAVENA, P., & SICA, A. (2002) · Trends in Immunology · doi:10.1016/s1471-4906(02)02302-5 · Cited by 5,528
Normalization of Tumor Vasculature: An Emerging Concept in Antiangiogenic Therapy
Jain, R. K. (2005) · Science · doi:10.1126/science.1104819 · Cited by 5,527 · cited 1×
“This is in accordance with the concept suggesting that antiangiogenic agents may temporarily lead to “normalization” of aberrant tumor vasculature, resulting in more efficient delivery of drugs and oxygen to the tumor.(39,40) In a recent trial, addition of the antiangiogenic integrininhibitor cilengitide appears to co…”
ResultTransformation from committed progenitor to leukaemia stem cell initiated by MLL–AF9
Krivtsov, A. V., Twomey, D., Feng, Z., Stubbs, M. C., Wang, Y., Faber, J., Levine, J. E., Wang, J., Hahn, W. C., Gilliland, D. G., et al. (2006) · Nature · doi:10.1038/nature04980 · Cited by 1,513 · cited 4×
“As an independent predictive factor of resistance, we have identified a HOX-dominated gene cluster, evocative of a self-renewal signature recently described for leukemia.(9) Strong HOXA10 expression of glioblastoma-derived neurospheres is in line with a role of HOX genes in the glioma stem-like cell compartment.”
BackgroundResultInfluentialThe role of human glioma-infiltrating microglia/macrophages in mediating antitumor immune responses1
Hussain, S. F., Yang, D., Suki, D., Aldape, K., Grimm, E., & Heimberger, A. B. (2006) · Neuro-Oncology · doi:10.1215/15228517-2006-008 · Cited by 592
Cited by
Comprehensive genomic characterization defines human glioblastoma genes and core pathways
The Cancer Genome Atlas Research Network (2008) · Nature · doi:10.1038/nature07385 · Cited by 7,735
Verhaak, R. G. W., Hoadley, K. A., Purdom, E., Wang, V., Qi, Y., Wilkerson, M. D., Miller, C. R., Ding, L., Golub, T., Mesirov, J. P., et al. (2010) · Cancer Cell · doi:10.1016/j.ccr.2009.12.020 · Cited by 7,575
Wen, P. Y., & Kesari, S. (2008) · New England Journal of Medicine · doi:10.1056/nejmra0708126 · Cited by 3,511
CSF-1R inhibition alters macrophage polarization and blocks glioma progression
Pyonteck, S. M., Akkari, L., Schuhmacher, A. J., Bowman, R. L., Sevenich, L., Quail, D. F., Olson, O. C., Quick, M. L., Huse, J. T., Teijeiro, V., et al. (2013) · Nature Medicine · doi:10.1038/nm.3337 · Cited by 2,463
Intrinsic Gene Expression Profiles of Gliomas Are a Better Predictor of Survival than Histology
Gravendeel, L. A. M., Kouwenhoven, M. C. M., Gevaert, O., de Rooi, J. J., Stubbs, A. P., Duijm, J. E., Daemen, A., Bleeker, F. E., Bralten, L. B. C., Kloosterhof, N. K., et al. (2009) · Cancer Research · doi:10.1158/0008-5472.can-09-2307 · Cited by 678
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Metadata
- Authors
- Murat, A., Migliavacca, E., Gorlia, T., Lambiv, W. L., Shay, T., Hamou, M.-F., de Tribolet, N., Regli, L., Wick, W., Kouwenhoven, M. C. M., Hainfellner, J. A., Heppner, F. L., Dietrich, P.-Y., Zimmer, Y., Cairncross, J. G., Janzer, R.-C., Domany, E., Delorenzi, M., Stupp, R., & Hegi, M. E.
- Venue
- Journal of Clinical Oncology
- Published
- 2008-06-20
- Volume
- 26
- Issue
- 18
- Pages
- 3015-3024
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- OpenAlex
- W2121625674
- Cited by
- 721
- References
- 7
- FWCI
- 20.21
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Murat, A., Migliavacca, E., Gorlia, T., Lambiv, W. L., Shay, T., Hamou, M.-F., de Tribolet, N., Regli, L., Wick, W., Kouwenhoven, M. C. M., Hainfellner, J. A., Heppner, F. L., Dietrich, P.-Y., Zimmer, Y., Cairncross, J. G., Janzer, R.-C., Domany, E., Delorenzi, M., Stupp, R., & Hegi, M. E. (2008). Stem Cell–Related “Self-Renewal” Signature and High Epidermal Growth Factor Receptor Expression Associated With Resistance to Concomitant Chemoradiotherapy in Glioblastoma. Journal of Clinical Oncology. https://doi.org/10.1200/jco.2007.15.7164
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
