Dataset Information

O-glycoproteomic datasets on the serum samples from patients with colorectal cancer

ABSTRACT: Clinical O-glycoproteomics for the development of diagnostic marker for colorectal cancer based on changes in O-glycosylation of serum protein.

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Daisuke Takakura

PROVIDER: PXD035279 | JPOST Repository | Thu Jul 13 00:00:00 BST 2023

REPOSITORIES: jPOST

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Publications

Targeted O-glycoproteomics for the development of diagnostic markers for advanced colorectal cancer.

Takakura Daisuke D Ohashi Shoko S Kobayashi Noritoshi N Tokuhisa Motohiko M Ichikawa Yasushi Y Kawasaki Nana N

Frontiers in oncology 20230209

Aberrant glycosylation is a prominent feature of cancer, that can be used as targets to improve the existing cancer biomarkers, and help to assess metastasis risks, and therapeutic effects. We developed a targeted O-glycoproteomics method using serum specimens, and evaluated its utility in identifying advanced colorectal cancer (CRC) markers. To this end, we combined consecutive lectin affinity purification using <i>Maclura pomifera</i> lectin (MPL), jacalin, and <i>Sambucus nigra</i> lectin, wh ...[more]

PMID: 36845686

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Project description:Colorectal cancer, one of the most frequent types of malignancy in the Western world, develops through a multi-step process. The main pathways establishing transformation of normal mucosa to invasive carcinoma include chromosomal instability (CIN), microsatellite instability (MSI) or epigenetic silencing through the CpG Island Methylator Phenotype (CIMP). These pathways have distinct clinical, pathological and genetic characteristics. In general, altered cell surface glycosylation has been linked to colorectal cancer progression, however the impact of MSI-specific pathways on the glycosylation machinery of MSI colon cancer cells has not been investigated yet. In a recent study (Patsos et al., 2009) we have shown that MSI-specific mutations induce marked alterations in cell surface glycosylation, indicating specific changes in the expression of glyco-genes. Therefore the purpose of our experiment is to define these changes by glyco-gene chip analysis. Biallelic mutational inactivation of MSI target genes is believed to drive MSI tumorigenesis. TGFBR2, ACVR2 and AIM2 are among the most frequently mutated genes in MSI colorectal adenomas and carcinomas and functional studies indicate their contribution to MSI-carcinogenesis. A first general screening approach by lectin FACS analysis indicated a correlation between functional inactivation of these genes and cell surface glycosylation of the MSI colon cell line HCT116 (Patsos et al., 2009). For detailed analysis of the altered glycosylation pattern and the underlying molecular mechanisms we have established HCT116 double stable transfectants that allow doxycycline-inducible expression of the three MSI target genes TGFBR2, ACVR2 and AIM2 in a reversible manner. Thus we can experimentally control the expression of the MSI-genes and analyze short and long-term effects on different cell functions, including glycosylation. From the application of the glyco-gene chip for analysis of the transfectants we expect to gain seminal information on the influence of MSI-target genes on glycan expression and function in MSI tumor cells. Correlating loss-of-function of MSI target genes not yet linked with glycosylation to the regulation of the glycophenotype is a novel approach to investigate the glycobiology of tumor cells. In addition it is also suitable to detect new MSI-(glyco)markers for clinical applications, including diagnostic tumor markers and specific targets for immunotherapies.

Project description:Changes in IgG glycosylation have been reported to be associated with colorectal cancer (CRC), but the alteration in specific subclass of IgG is unknown. Herein, we optimized five common IgG glycopeptides enrichment methods to acquire comprehensive profiling of IgG glycoproteomics in CRC. Notably, incomplete tryptic digestion of IgG occurred when using ordinary ratio of protease to protein, which significantly impacted the final statistical analysis of association between IgG glycosylation and CRC. We introduced a method based on two-step enzymatic digestion, enabling the complete digestion of IgG glycopeptides and further improving the detection intensity of the target glycopeptides. By this approach, total 47 IgG glycopeptides can be identified by nanoLC-ESI-MS/MS. Following rapid and automatic data processing through the self-developed program, we observed that IgG1_H3N4F1 and IgG1_H3N4 were substantially increased in CRC, while IgG1_H5N5F1, IgG1_H5N4F1S1and IgG2_H5N4F1 were markedly decreased. Strikingly, these four glycopeptides were continually significantly changed in early and late stages of CRC. Further evaluation of the diagnostic performance showed they all obtained a fair performance in discriminating the patients from the normal. In terms of the glycan features, it demonstrated that CRC progression associates with the increased agalactosylation, and the decreased digalactosylation and galactosylation per antenna on diantennay glycans of IgG1 and IgG2. Concurrently, the decreased sialylation of IgG1 was strongly correlated with CRC. Moreover, tumor-specific glycosylation analysis showed that the alterations of subclass-specific IgG glycosylation were more significant in colon cancer, and no obvious difference between colon and rectal cancer was found. More importantly, all these findings were validated in an independent cohort. This two-step enzymatic approach is crucial to explore the relationship between the disease progression and IgG glycosylation.

Dataset Information

O-glycoproteomic datasets on the serum samples from patients with colorectal cancer

Publications

Targeted O-glycoproteomics for the development of diagnostic markers for advanced colorectal cancer.

Similar Datasets

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