Tumour-associated circulating microparticles: A novel liquid biopsy tool for screening and therapy monitoring of colorectal carcinoma and other epithelial neoplasia

Abstract

Up to date, novel tools for low-cost, minimal invasive cancer surveillance, cancer screening and treatment monitoring are in urgent need. Physicians consider the so-called liquid biopsy as a possible future tool successfully achieving these ultimate goals. Here, we aimed to identify circulating tumour-associated MPs (taMPs) that could aid in diagnosing minimal-invasively the presence and follow up treatment in non-small cell lung carcinoma (NSCLC), colorectal carcinoma (CRC) and pancreas carcinoma (PaCa). Tumour-associated MPs (taMPs) were quantified after isolation by centrifugation followed by flow cytometry analysis from the serum of cancer patients with CRC (n = 52), NSCLC (n = 40) and PaCa (n = 11). Healthy subjects (n = 55) or patients with struma nodosa (thyroid nodules) (n = 43) served as negative controls. In all three types of tumour entities, the presence of tumour was associated with an increase of circulating EpCAM⁺ and EpCAM⁺CD147⁺ taMPs. The presence of CD147⁺EpCAM⁺ taMPs were specific to tumour-bearing patients thus allowing the specific distinction of malignancies from patients with thyroid nodules. Increased level of EpCAM single positive MPs were, in turn, also detected in patients with thyroid nodules. Importantly, EpCAM⁺CD147⁺ taMPs correlated with the measured tumour-volume in CRC patients. EpCAM⁺ taMPs decreased at 7 days after curative R0 tumour resection suggesting a close dependence with tumour presence. AUROC values (up to 0.85 and 0.90), sensitivity/specificity scores, and positive/negative predictive values indicated a high diagnostic accuracy of EpCAM⁺CD147⁺ taMPs. Taken together, EpCAM⁺CD147⁺ double positive taMPs could potentially serve as novel promising clinical parameter for cancer screening, diagnosis, surveillance and therapy monitoring.