Biology subjects

Ahn, S. B.

Publications and source records attributed to Ahn, S. B..

3 recordsLinked to original sources

bioRxiv2024

Tumor- and immune-derived N-acetyl-β-D-hexosaminidase drive colorectal cancer and stratify patient risk

Non-invasive prognostic markers are needed to improve survival of colorectal cancer (CRC) patients. Towards this goal, we applied integrative systems glycobiology approaches to tumor tissues and PBMCs from CRC patients and matching controls as well as to a CRC patient-derived cell line. Firstly, quantitative glycomics and glycoproteomics revealed that non-canonical paucimannosidic proteins from monocytic and cancer cell origins are prominent signatures in CRC tumor tissues, and that their expression associates with CRC progression. Guided by these associations, we then showed that N-acetyl-{beta}-D-hexosaminidase (Hex) facilitates paucimannosidic protein biosynthesis in CRC cells and is intimately involved in processes underpinning CRC metastasis (adhesion, migration, invasion, proliferation). Finally, Hex activity was found to be elevated in PBMCs and plasma from patients with advanced CRC relative to matching controls while plasma Hex activity correlated strongly with CRC patient survival. Our study opens avenues for better prognostication, disease risk stratification and therapeutic interventions in CRC. HighlightsO_LI* Non-canonical truncated glycans of immune and cancer origins dominate in CRC tumors C_LIO_LI* N-acetyl-{beta}-D-hexosaminidase, a truncating glycoenzyme, drives tumorigenesis in CRC C_LIO_LI* Activity of plasma N-acetyl-{beta}-D-hexosaminidase stratifies risk in CRC patients C_LI

cancer biology↗

bioRxiv2022

IDENTIFICATION AND QUANTIFICATION OF MATRISOME PROTEINS OF MOUSE KIDNEYS

Extracellular matrix (ECM) is essential for tissue homeostasis. Understanding the matrisome (ECM proteome) composition and mechanisms of ECM control in health and disease is crucial for discovering therapeutic agents and diagnostic tools for inflammatory, fibrotic and cancerous conditions. The challenging obstacle in the ECM analysis is the need to optimise matrisome enrichment methods for different organs, diseases, and species. Currently, there is no optimized protocol nor a publicly available matrisome database for mouse kidneys. This limits the power of murine models in renal diseases and development research. In this study, we comparatively explored the matrisome of healthy C57BL/6 mice using two matrisome extraction methods, including the Millipore Compartment Fractionation (Method-1) and the Sequential Extraction (Method-2) approaches. We examined the efficiency of these methods in matrisome profiling by LC-MS/MS, protein identification and label-free quantification using MaxQuant. As a result of the study, 113 matrisome proteins were identified, including 22 proteins that have not been previously listed in the Matrisome Database (MD). Method-2 allowed identification and quantification of all core and ECM-associated matrisome proteins detected by Method-1 and additionally revealed more core matrisome and ECM-associated proteins. By characterisation of the murine renal matrisome enhanced by our methodological insights, this study provides critically important information for biological and medical kidney research.

molecular biology↗

bioRxiv2020

A Recombinant Protein Biomarker DDA Library Increases DIA Coverage of Low Abundance Plasma Proteins

Credible detection and quantification of low abundance proteins from human blood plasma is a major challenge in precision medicine biomarker discovery when using mass spectrometry (MS). Here, we employed a mixture of recombinant proteins in DDA libraries to subsequently detect cancer-associated low abundance plasma proteins using SWATH/DIA. The exemplar DDA recombinant protein spectral library (rPSL) was derived from tryptic digestion of 36 human recombinant proteins that had been previously implicated as possible cancer biomarkers in both our own and other studies. The rPSL was then used to identify proteins from non-depleted colorectal cancer (CRC) plasmas by SWATH-MS. Most (32/36) of the proteins in the rPSL were reliably identified in plasma samples, including 8 proteins (BTC, CXCL10, IL1B, IL6, ITGB6, TGF, TNF, TP53) not previously detected using high-stringency MS in human plasmas according to PeptideAtlas. The rPSL SWATH-MS protocol was compared to DDA-MS using MARS-depleted and post-digestion peptide fractionated plasmas (here referred to as a human plasma DDA library). Of the 32 proteins identified using rPSL SWATH, only 12 were identified using DDA-MS. The 20 additional proteins exclusively identified by using the rPSL approach with SWATH were mostly lower abundance (i.e., <10ng/ml) plasma proteins. To mitigate FDR concerns, and replicating a more typical approach, the DDA rPSL was also merged into a human plasma DDA library. When SWATH identification was repeated using this merged library, the majority (33/36) of low abundance plasma proteins from the rPSL could still be identified using high-stringency HPP Guidelines v3.0 protein inference criteria.

biochemistry↗