Spatial UBE2N protein expression indicates genomic instability in colorectal cancers

Area of Science:

• Oncology
• Proteomics
• Molecular Pathology

Background:

• Colorectal cancer (CRC) is characterized by genomic instability, leading to tumor heterogeneity and treatment resistance.
• Imaging mass spectrometry (IMS) offers a powerful approach to analyze spatial protein distribution in tissues for phenotype investigation.

Purpose of the Study:

• To investigate the potential of IMS for molecular classification of colorectal cancers.
• To identify protein biomarkers distinguishing different CRC subtypes.

Main Methods:

• Analysis of a tissue microarray of 60 CRCs and control tissues using IMS.
• Protein profiles were obtained from tissue sections, followed by liquid chromatography-mass spectrometry identification.
• Validation of identified biomarkers using immunohistochemistry on initial and independent sample sets.

Main Results:

• Twenty-eight mass-to-charge ratio (m/z) values differentiated euploid from aneuploid CRCs (p < 0.001).
• UBE2N protein was validated as a distinguishing marker, showing significant differences between euploid and aneuploid CRCs in both initial (p = 0.0274) and independent (p = 0.0070) cohorts.

Conclusions:

• FFPE protein expression profiling using MALDI-TOF MS holds promise for improved molecular classification of CRC.
• UBE2N protein expression serves as a validated biomarker for distinguishing euploid from aneuploid colorectal cancers.