A subset of metzincins and related genes constitutes a marker of human solid organ fibrosis

Rödder, Silke; Scherer, Andreas; Körner, Meike; Marti, Hans-Peter (2011). A subset of metzincins and related genes constitutes a marker of human solid organ fibrosis. Virchows Archiv, 458(4), pp. 487-96. Berlin: Springer-Verlag 10.1007/s00428-011-1052-7

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute of Pathology
04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Nephrology and Hypertension

UniBE Contributor:

Körner Jachertz, Meike and Marti, Hans-Peter

ISSN:

0945-6317

Publisher:

Springer-Verlag

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:18

Last Modified:

24 Oct 2019 20:26

Publisher DOI:

10.1007/s00428-011-1052-7

PubMed ID:

21337037

Web of Science ID:

000288656400011

BORIS DOI:

10.7892/boris.5521

URI:

https://boris.unibe.ch/id/eprint/5521 (FactScience: 210274)

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