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Spatial UBE2N protein expression indicates genomic instability in colorectal cancers
- 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.
- Subjects :
- 0301 basic medicine
Genome instability
Genomic instability
Male
Proteomics
Cancer Research
Aneuploidy
Biology
lcsh:RC254-282
Protein expression
Mass spectrometry imaging
Cohort Studies
03 medical and health sciences
0302 clinical medicine
Imaging mass spectrometry
Surgical oncology
Tandem Mass Spectrometry
Genetics
medicine
Biomarkers, Tumor
Humans
Tissue Distribution
Aged
Tissue microarray
Middle Aged
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
medicine.disease
Phenotype
Immunohistochemistry
UBE2N
030104 developmental biology
Oncology
ROC Curve
030220 oncology & carcinogenesis
Area Under Curve
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
Ubiquitin-Conjugating Enzymes
Cancer research
Female
Colorectal Neoplasms
Research Article
Chromatography, Liquid
Subjects
Details
- Language :
- English
- ISSN :
- 14712407
- Volume :
- 19
- Database :
- OpenAIRE
- Journal :
- BMC Cancer
- Accession number :
- edsair.doi.dedup.....7d51bbd1a7687869480e3e2c890001e7