COL10A1 as a component of lateral information cascade to drive invasion & metastasis of colon cancer

Introduction Collagen type X alpha 1 chain (COL10A1) has been discussed as a diagnostic biomarker for colon cancer (CC). Published work does ignore state of the art molecular technologies nor appreciates intra-/inter tumoral heterogeneity and patient diversity. Lateral transfer of information carriers from components of the extracellular matrix onto cancer cells emerges as a potent driver mechanisms of tumor progression, but little is known whether COL10A1 presents a potent component in this context

Aims Investigate the potency COL10A1 in cancer associated fibroblasts to mediate any pro-tumorigenic lateral information flow onto cancer cells and identify putative downstream mechanisms. Assess the clinical predictive potential of CC COL10A1 utilizing state of the art molecular technologies to predict lymph node metastatic spread and clinical course of patients.

Methods Various bioinformatic assay, protein-protein interaction modeling, CRISPR/Cas gene editing in vitro, co-culture assay,

Results COL10A1 mRNA in clinical CR samples is upregulated compared to normal colon. Protein-interaction modelling suggests association of elevated COL10A1 to stemness and epithelial-to-mesenchymal transformation (EMT). COL10A1 in clinical CR samples is associated to perineural invasion and lymphatic invasion. COL10A1 is elevated in Caucasian patients compared to other ethnicities. Elevated COL10A1 mRNA significantly associates to CAFs consensus signature and to altered immune checkpoint expression levels. COL10A1 is elevated in fibroblasts with model development ongoing.

Conclusion COL10A1 mRNA and protein levels in CC tissue serve as clinical predictive markers for metastatic potential and might present therapeutic target of the cancer microenvironment. The conduction of a prospective clinical trial to validate the diagnostic value of COL10A1 is warranted and may help to personalize surgical management of CC patients with synchronic liver metastasis.

Publication History

Article published online:
19 August 2022