E-selectin Affinity Glycoproteomics Reveals Neuroendocrine Proteins and the Secretin Receptor as a Poor Prognosis Signature in Colorectal Cancer

ABSTRACT: Colorectal cancer (CRC) cells express glycoproteins with sialylated Lewis antigens (sLe), crucial for metastasis via E-selectin binding. However, these glycoepitopes lack cancer specificity, and E-selectin-targeted glycoproteins are unknown. Here we established a framework for identifying metastasis-linked glycoproteoforms for precision oncology. We found that over 70% of colorectal tumours overexpressed sLeA/X, yet without association with metastasis or survival. This prompted deeper exploration on the sialoglycoproteome of metastatic tumours. Nearly 600 glycoproteins were identified using E-selectin affinity enrichment and mass spectrometry, significantly broadening our understanding of potential metastasis-related glycoproteins. This glycoproteome was linked to cell adhesion, active transport of molecules and ions across the plasma membrane, oncogenic pathways, angiogenesis, and, unexpectedly, neuroendocrine functions. Employing an in-house algorithm for targetability prioritization, the less studied secretin receptor (SCTR) emerged as a top-ranked glycoprotein. The screening of tumours confirmed SCTR's association with poor prognosis and metastasis. N-glycosylation carrying sLe antigens added cancer specificity to SCTR. Prognostic links were reinforced by TCGA-based investigations. In summary, SCTR, a relatively unknown CRC glycoprotein, holds potential as a biomarker of poor prognosis and as a E-selectin ligand, suggesting an unforeseen role in metastasis warranting confirmation. Future investigations should also focus on this glycoproteoforms’ biological foreseeing clinical applications.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Colon

SUBMITTER: Marta Relvas-Santos  

LAB HEAD: José Alexandre Ferreira

PROVIDER: PXD054727 | Pride | 2024-11-11

REPOSITORIES: Pride