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Detection of a Circulating MicroRNA Custom Panel in Patients with Metastatic Colorectal Cancer

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HEXB Drives Raised Paucimannosylation in Colorectal Cancer and Stratifies Patient Risk.

Rebeca Kawahara¹, Liisa Kautto², Naaz Bansal²

¹School of Natural Sciences, Macquarie University, Sydney, New South Wales, Australia; Institute for Glyco-core Research (iGCORE), Nagoya University, Nagoya, Aichi, Japan.

Molecular & Cellular Proteomics : MCP

|February 13, 2025

Summary

Elevated N-acetyl-β-D-hexosaminidase (Hex) activity in plasma is a novel biomarker for colorectal cancer (CRC) prognosis. This finding aids in stratifying CRC patient risk and improving survival outcomes.

Keywords:

HEXB colorectal cancer glycoproteomics glycosylation survival

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Area of Science:

Glycobiology
Cancer Research
Biomarker Discovery

Background:

Noninvasive prognostic markers are crucial for improving colorectal cancer (CRC) patient survival.
Current prognostic tools require enhancement for better disease risk stratification.

Purpose of the Study:

To identify novel noninvasive molecular markers for colorectal cancer (CRC) prognosis using systems glycobiology.
To investigate the role of N-acetyl-β-D-hexosaminidase (Hex) in CRC and its potential as a prognostic indicator.

Main Methods:

Untargeted systems glycobiology approaches applied to CRC tissues and peripheral blood mononuclear cells.
Quantitative glycomics, immunohistochemistry, and glycoproteomics were employed.
Development and application of a sensitive enzyme activity assay for Hex in plasma and cells.

Main Results:

Noncanonical paucimannosidic N-glycans are elevated in CRC tumors.
N-acetyl-β-D-hexosaminidase subunit β (HEXB) is overexpressed in CRC tissues and facilitates paucimannosidic protein biosynthesis.
Elevated Hex activity in plasma and peripheral blood mononuclear cells correlates with advanced CRC stage and poorer 5-year survival.

Conclusions:

Elevated plasma Hex activity serves as a potential disease risk marker for colorectal cancer (CRC) patient outcome.
These glycoproteomics-driven findings offer new avenues for CRC prognostication and risk stratification.