title: A subset of metzincins and related genes constitutes a marker of human solid organ fibrosis.
abstract: Metzincins and functionally related genes play important roles in extracellular matrix remodeling both in healthy and fibrotic conditions. We recently presented a transcriptomic classifier consisting of 19 metzincins and related genes (MARGS) discriminating biopsies from renal transplant patients with or without interstitial fibrosis/tubular atrophy (IF/TA) by virtue of gene expression measurement (Roedder et al., Am J Transplant 9:517-526, 2009). Here we demonstrate that the same algorithm has diagnostic value in non-transplant solid organ fibrosis. We used publically available microarray datasets of 325 human heart, liver, lung, kidney cortex, and pancreas microarray samples (265 with fibrosis, 60 healthy controls). Expression of nine commonly differentially expressed genes was confirmed by TaqMan low-density arrays (Applied Biosystems, USA) in 50 independent archival tissue specimens with matched histological diagnoses to microarray patients. In separate and in combined, integrated microarray data analyses of five datasets with 325 samples, the previously published MARGS classifier for renal post-transplant IF/TA had a mean AUC of 87% and 82%, respectively. These data demonstrate that the MARGS gene panel classifier not only discriminates IF/TA from normal renal transplant tissue, but also classifies solid organ fibrotic conditions of human pancreas, liver, heart, kidney, and lung tissue samples with high specificity and accuracy, suggesting that the MARGS classifier is a cross-platform, cross-organ classifier of fibrotic conditions of different etiologies when compared to normal tissue.
authors.affiliation: Department of Nephrology and Hypertension, Inselspital, University of Bern, Freiburgstrasse 15, 3010, Bern, Switzerland.
authors.forename: Silke
authors.initials: S
authors.lastname: Rödder
authors.forename: Andreas
authors.initials: A
authors.lastname: Scherer
authors.forename: Meike
authors.initials: M
authors.lastname: Körner
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Marti
mesh_terms: D051722:ADAM Proteins / Q000096:biosynthesis / Q000235:genetics; D000465:Algorithms; D019540:Area Under Curve; D015415:Biomarkers / Q000032:analysis*; D005355:Fibrosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D020869:Gene Expression Profiling; D006331:Heart Diseases / Q000235:genetics / Q000473:pathology; D006801:Humans; D007674:Kidney Diseases / Q000235:genetics / Q000473:pathology; D008107:Liver Diseases / Q000235:genetics / Q000473:pathology; D008171:Lung Diseases / Q000235:genetics / Q000473:pathology; D020782:Matrix Metalloproteinases / Q000096:biosynthesis / Q000235:genetics; D008666:Metalloendopeptidases / Q000096:biosynthesis / Q000235:genetics; D046228:Microarray Analysis; D010182:Pancreatic Diseases / Q000235:genetics; D012372:ROC Curve; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D015415:Biomarkers; D051722:ADAM Proteins; D020782:Matrix Metalloproteinases; D008666:Metalloendopeptidases; C095666:serralysin