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Spatial UBE2N protein expression indicates genomic instability in colorectal cancers

Authors :
Oliver Klein
Timo Gemoll
Annette Lischka
Christoph Thorns
Elena Miroll
Jens K. Habermann
Murat Eravci
Source :
BMC Cancer, BMC Cancer, Vol 19, Iss 1, Pp 1-8 (2019)
Publication Year :
2019
Publisher :
BioMed Central, 2019.

Abstract

Background One major hallmark of colorectal cancers (CRC) is genomic instability with its contribution to tumor heterogeneity and therapy resistance. To facilitate the investigation of intra-sample phenotypes and the de novo identification of tumor sub-populations, imaging mass spectrometry (IMS) provides a powerful technique to elucidate the spatial distribution patterns of peptides and proteins in tissue sections. Methods In the present study, we analyzed an in-house compiled tissue microarray (n = 60) comprising CRCs and control tissues by IMS. After obtaining protein profiles through direct analysis of tissue sections, two validation sets were used for immunohistochemical evaluation. Results A total of 28 m/z values in the mass range 800–3500 Da distinguished euploid from aneuploid CRCs (p 0.635). After liquid chromatograph-mass spectrometry identification, UBE2N could be successfully validated by immunohistochemistry in the initial sample cohort (p = 0.0274, ROC AUC = 0.7937) and in an independent sample set of 90 clinical specimens (p = 0.0070, ROC AUC = 0.6957). Conclusions The results showed that FFPE protein expression profiling of surgically resected CRC tissue extracts by MALDI-TOF MS has potential value for improved molecular classification. Particularly, the protein expression of UBE2N was validated in an independent clinical cohort to distinguish euploid from aneuploid CRCs. Electronic supplementary material The online version of this article (10.1186/s12885-019-5856-1) contains supplementary material, which is available to authorized users.

Details

Language :
English
ISSN :
14712407
Volume :
19
Database :
OpenAIRE
Journal :
BMC Cancer
Accession number :
edsair.doi.dedup.....7d51bbd1a7687869480e3e2c890001e7