title: Association of collagen architecture with glioblastoma patient survival.
abstract: OBJECTIVE Glioblastoma (GBM) is the most malignant primary brain tumor. Collagen is present in low amounts in normal brain, but in GBMs, collagen gene expression is reportedly upregulated. However, to the authors' knowledge, direct visualization of collagen architecture has not been reported. The authors sought to perform the first direct visualization of GBM collagen architecture, identify clinically relevant collagen signatures, and link them to differential patient survival. METHODS Second-harmonic generation microscopy was used to detect collagen in a GBM patient tissue microarray. Focal and invasive GBM mouse xenografts were stained with Picrosirius red. Quantitation of collagen fibers was performed using custom software. Multivariate survival analysis was done to determine if collagen is a survival marker for patients. RESULTS In focal xenografts, collagen was observed at tumor brain boundaries. For invasive xenografts, collagen was intercalated with tumor cells. Quantitative analysis showed significant differences in collagen fibers for focal and invasive xenografts. The authors also found that GBM patients with more organized collagen had a longer median survival than those with less organized collagen. CONCLUSIONS Collagen architecture can be directly visualized and is different in focal versus invasive GBMs. The authors also demonstrate that collagen signature is associated with patient survival. These findings suggest that there are collagen differences in focal versus invasive GBMs and that collagen is a survival marker for GBM.
authors: Departments of 1 Neurological Surgery and.|Cellular and Molecular Biology Graduate Program.|Laboratory for Optical and Computational Instrumentation.
authors: Kelli B
authors: KB
authors: Pointer
authors: Departments of 1 Neurological Surgery and.
authors: Paul A
authors: PA
authors: Clark
authors: Laboratory for Optical and Computational Instrumentation.|Medical Physics Graduate Program.|Morgridge Institute for Research; and.
authors: Alexandra B
authors: AB
authors: Schroeder
authors: Pathology and Laboratory Medicine.|Carbone Cancer Center, University of Wisconsin, Madison, Wisconsin; and.
authors: M Shahriar
authors: MS
authors: Salamat
authors: Cellular and Molecular Biology Graduate Program.|Laboratory for Optical and Computational Instrumentation.|Medical Physics Graduate Program.|Morgridge Institute for Research; and.|Carbone Cancer Center, University of Wisconsin, Madison, Wisconsin; and.
authors: Kevin W
authors: KW
authors: Eliceiri
authors: Departments of 1 Neurological Surgery and.|Cellular and Molecular Biology Graduate Program.|Carbone Cancer Center, University of Wisconsin, Madison, Wisconsin; and.|Department of Surgery, National University of Singapore, Singapore.
authors: John S
authors: JS
authors: Kuo
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D003094:Collagen / Q000378:metabolism*; D005260:Female; D005909:Glioblastoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D011379:Prognosis; D015996:Survival Rate
chemical_list: D003094:Collagen
keywords: ECM = extracellular matrix; GBM = glioblastoma; GSC = GBM stem-like cell; KPS = Karnofsky Performance Scale; LOCI = Laboratory for Optical and Computational Instrumentation; NOD SCID = nonobese diabetic severe combined immunodeficient; SHG = second-harmonic generation; TMA = tissue microarray; biomarker; cancer stem-like cells; collagen; glioblastoma; oncology; second-harmonic generation