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.

Monitoring Therapy Efficiency in Cancer through Extracellular Vesicles

“…MPs correlated with the tumor-volume. At 7 days post-op, Willms et al saw a significant decrease of MPs [40].…”

“…Nevertheless, there is increasing interest in developing methods to improve monitoring accuracy for post-operative recurrence and for therapy monitoring of non-operative options. Willms et al [40] ( Table 1) could show that curative total tumor R0 resection altered tumor-associated microparticles (taMPs). The group analyzed EpCAM and CD147, as common cancer antigens, on taMPs in 52 CRC patients.…”

Extracellular Vesicles in Liver Diseases: Meeting Report from the International Liver Congress 2018

“…Therefore, the tumor‐associated (ta) EVs, also known as taMVs/taMPs, might help in the detection/diagnosis of cancer. Evidence suggests that EV shedding is not dependent on a metastatic cancer phenotype . Therefore, the use of EVs as an advanced tool for a novel kind of liquid biopsy marker eventually revealing tumor presence, entity, location, and stage/diameter might be possible.…”

“…Evidence suggests that EV shedding is not dependent on a metastatic cancer phenotype. (48) Therefore, the use of EVs as an advanced tool for a novel kind of liquid biopsy marker eventually revealing tumor presence, entity, location, and stage/diameter might be possible. However, a main challenge is the quest for specific antigens on EVs that could help in the identification of specific EVs derived from the cancer cells (Fig.…”

“…(7) These data suggest that the simultaneous combination of cancer cell-derived antigens in MVs might be useful in the diagnosis of specific cancer entities. This approach resulted first in the use of a pan-cancer marker based on epithelial cell adhesion molecule (EpCAM) + CD147 + MPs/MVs (48) that was further refined and validated for the diagnosis of hepatobiliary tumors, such as HCC and CCA. (47) In fact, it was confirmed that AnnexinV + EpCAM + CD147 + MVs/MPs were elevated in HCC and CCA as in other investigated tumor entities and that asialoglycoprotein receptor 1 (ASGPR1) + AnnexinV + EpCAM + CD133 + was more specific for hepatic disorders, such as nonmalignant cirrhosis (liver fibrosis F4 stage), HCC, and CCA.…”