Circulating multi-omic signature of disease severity and cholangiocarcinoma in primary sclerosing cholangitis.

What To Know

This paper reports an analysis of plasma ‘multi-omics’ (proteins, metabolites, and miRNAs) measured in 33 people with primary sclerosing cholangitis (PSC) to find circulating signatures linked to disease severity and to cholangiocarcinoma (CCA).

The authors used machine-learning and network modeling to integrate data and performed pathway enrichment on features identified by both approaches.

They found multi-omic patterns associated with PSC severity, with overlaps between severe PSC and PSC-associated CCA, including immune- and epithelial-interacting proteins, bile acid and glutathione-related metabolites, and miRNAs involved in fibrosis, inflammation, extracellular matrix remodeling, and cell-cycle regulation.

In established PSC-CCA they report coordinated changes in oncogenic miRNAs, growth factor–related proteins, and depletion of certain metabolites consistent with altered detoxification and an inflammatory, pro-tumor microenvironment.