An EV proteome signature for non-invasive risk stratification and early-response evaluation of colorectal liver metastases

Preoperative risk stratification and chemotherapy-response prediction for patients with colorectal liver metastases (CRLM) remain areas of unmet clinical need. Patients with colorectal liver metastases (CRLM) have a 5-year overall survival (OS) of 25.2% compared to 75.1% of patients without metastases. Surgical resection of CRLM is an established treatment extending 5-year OS to 40–50%.

At present, molecular risk stratification of CRLM is based on histopathological assessment and prevalent drivers of disease derived from a tumour biopsy. Liquid biopsies, i.e. non-invasive analyses of circulating tumour-derived material, may provide unique information about the disease, and moreover, allow monitoring of tumour evolution in response to treatment.

Circulating extracellular vesicles (cEVs) are commonly found in body fluids. cEVs encapsulate various cargoes, including proteins, lipids and nucleic acids recapitulating molecular traits of its donor tissue. Mutational changes frequently observed in cancer were detected in cEVs of CRC patients on mRNA level. A differential abundance for distinct non-coding RNAs in cEVs in CRC compared to patients with benign disease have also been reported. cEVs have been suggested to be more stable compared to serological proteins as the lipid bilayer protects the content from proteases and other enzyme. In contrast to solid tumour biopsies, that are sampled from a single site, cEVs may provide unique information about the full metastatic complement.

A team led by researchers at Carl Gustav Carus University Hospital set out to identify a predictive signature based on the protein cargo of circulating extracellular vesicles (cEVs) and to validate this EV protein (EVP) signature in independent patient cohorts.

Lin K, Baenke F, Lai X, Schneider M, Helm D, Polster H, Rao VS, Ganig N, Wong FC, Seifert L, Seifert AM, Jahnke B, Kretschmann N, Ziemssen T, Klupp F, Schmidt T, Schneider M, Han Y, Weber TF, Plodeck V, Nebelung H, Schmitt N, Korell F, Köhler BC, Riediger C, Weitz J, Rahbari NN, Kahlert C. (2022) Comprehensive proteomic profiling of serum extracellular vesicles in patients with colorectal liver metastases identifies a signature for non-invasive risk stratification and early-response evaluation. Mol Cancer 21(1):91. [article]

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