TY - JOUR
T1 - Formalin-fixed paraffin-embedded renal biopsy tissues
T2 - an underexploited biospecimen resource for gene expression profiling in IgA nephropathy
AU - Cox, Sharon Natasha
AU - Chiurlia, Samantha
AU - Divella, Chiara
AU - Rossini, Michele
AU - Serino, Grazia
AU - Bonomini, Mario
AU - Sirolli, Vittorio
AU - Aiello, Francesca B.
AU - Zaza, Gianluigi
AU - Squarzoni, Isabella
AU - Gangemi, Concetta
AU - Stangou, Maria
AU - Papagianni, Aikaterini
AU - Haas, Mark
AU - Schena, Francesco Paolo
N1 - Funding Information:
This work was supported by grants from MIUR (COFIN-PRIN 2006069815; PONa3_00134) and from Puglia Region (BISIMANE project 44/2008).
Publisher Copyright:
© 2020, The Author(s).
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/12/1
Y1 - 2020/12/1
N2 - Primary IgA nephropathy (IgAN) diagnosis is based on IgA-dominant glomerular deposits and histological scoring is done on formalin-fixed paraffin embedded tissue (FFPE) sections using the Oxford classification. Our aim was to use this underexploited resource to extract RNA and identify genes that characterize active (endocapillary–extracapillary proliferations) and chronic (tubulo-interstitial) renal lesions in total renal cortex. RNA was extracted from archival FFPE renal biopsies of 52 IgAN patients, 22 non-IgAN and normal renal tissue of 7 kidney living donors (KLD) as controls. Genome-wide gene expression profiles were obtained and biomarker identification was carried out comparing gene expression signatures a subset of IgAN patients with active (N = 8), and chronic (N = 12) renal lesions versus non-IgAN and KLD. Bioinformatic analysis identified transcripts for active (DEFA4,TNFAIP6,FAR2) and chronic (LTB,CXCL6, ITGAX) renal lesions that were validated by RT-PCR and IHC. Finally, two of them (TNFAIP6 for active and CXCL6 for chronic) were confirmed in the urine of an independent cohort of IgAN patients compared with non-IgAN patients and controls. We have integrated transcriptomics with histomorphological scores, identified specific gene expression changes using the invaluable repository of archival renal biopsies and discovered two urinary biomarkers that may be used for specific clinical decision making.
AB - Primary IgA nephropathy (IgAN) diagnosis is based on IgA-dominant glomerular deposits and histological scoring is done on formalin-fixed paraffin embedded tissue (FFPE) sections using the Oxford classification. Our aim was to use this underexploited resource to extract RNA and identify genes that characterize active (endocapillary–extracapillary proliferations) and chronic (tubulo-interstitial) renal lesions in total renal cortex. RNA was extracted from archival FFPE renal biopsies of 52 IgAN patients, 22 non-IgAN and normal renal tissue of 7 kidney living donors (KLD) as controls. Genome-wide gene expression profiles were obtained and biomarker identification was carried out comparing gene expression signatures a subset of IgAN patients with active (N = 8), and chronic (N = 12) renal lesions versus non-IgAN and KLD. Bioinformatic analysis identified transcripts for active (DEFA4,TNFAIP6,FAR2) and chronic (LTB,CXCL6, ITGAX) renal lesions that were validated by RT-PCR and IHC. Finally, two of them (TNFAIP6 for active and CXCL6 for chronic) were confirmed in the urine of an independent cohort of IgAN patients compared with non-IgAN patients and controls. We have integrated transcriptomics with histomorphological scores, identified specific gene expression changes using the invaluable repository of archival renal biopsies and discovered two urinary biomarkers that may be used for specific clinical decision making.
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U2 - 10.1038/s41598-020-72026-2
DO - 10.1038/s41598-020-72026-2
M3 - Article
C2 - 32938960
AN - SCOPUS:85091045842
VL - 10
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
IS - 1
M1 - 15164
ER -