Enlarged extracellular vesicles are a negative prognostic factor in patients undergoing TACE for primary or secondary liver cancer–a case series

Abstract

Background Transarterial chemoembolization (TACE) has evolved as a standard treatment option in patients with intermediate stage, unresectable HCC [Barcelona Clinic Liver Cancer (BCLC) stage B] as well as in patients with liver metastases, when surgery or systemic therapy is considered not appropriate. Concentration and sizes of extracellular vesicles (EVs) recently emerged as novel diagnostic and prognostic biomarkers in patients with liver cancer, but no data on its prognostic relevance in the context of TACE exists. Here, we evaluate pre-interventional EVs as a potential biomarker in patients undergoing TACE for primary and secondary hepatic malignancies. Methods Vesicle size distribution and concentration were measured by nanoparticle tracking analysis (NTA) in patient sera before and after TACE in 38 patients. Results Extracellular vesicle size distribution measured before TACE is of prognostic significance with respect to overall survival in patients after TACE. Overall survival is significantly reduced when initial vesicle size (X50) is in the upper quartile (>145.65nm). Median overall survival in patients in the upper quartile was only 314 days, compared to 799 days in patients with vesicle size in the first to third quartile (<145.65nm; p = 0.007). Vesicle size was also shown to be a significant prognostic marker for overall survival in Cox regression analysis [HR 1.089, 95% CI: 1.021–1.162, p = 0.010]. In addition, a significant correlation was observed between initial EVs concentration/BMI (rS = 0.358, p = 0.029), X50/IL-8-concentration (rS = 0.409, p = 0.011) and X50/CRP-concentration (rS = 0.404, p = 0.016). In contrast, with regard to immediate tumor response after TACE, EVs concentration and size did not differ. Summary Sizes (but not concentrations) of EVs represent a novel prognostic marker in patients receiving TACE for primary and secondary hepatic malignancies since patients with enlarged EVs display a significantly impaired prognosis after TACE.

Plasma Pattern of Extracellular Vesicles Isolated from Hepatitis C Virus Patients and Their Effects on Human Vascular Endothelial Cells

“…Instead, no differences were observed between HCV patients and healthy controls as regarding the concentration of EVs ( Figure 1 C,D). These results are in agreement with previous reports showing that EVs sizes rather than EVs concentrations are increased in liver failure patients and correlate with prognosis [ 24 , 25 , 26 , 27 ].…”

“…The same applies to chronic viral hepatitis B, where both large [ 50 ] and small EVs [ 51 , 52 ] were reported. In any case, it is noteworthy that sizes rather than the concentrations of EVs were found to be correlated with the prognosis of such different conditions as acute liver failure [ 25 ], cirrhosis [ 26 ], and/or HCC [ 27 ], providing evidence for their previously unrecognized role as biomarkers also in this specific context.…”

Extracellular Vesicles as Markers of Liver Function: Optimized Workflow for Biomarker Identification in Liver Disease

“…To the best of our knowledge, the current work is the first to report a quantitative analysis of the distribution of EVs in patients with chronic liver disease, and it supports the conclusion that analysis of EVs in crude serum might provide prognostic or diagnostic information. In this regard, we have recently shown that EVs sizes represent a novel prognostic marker in patients receiving transarterial chemoembolization (TACE) for primary and secondary hepatic malignancies [34].…”

An optimized workflow for analyzing extracellular vesicles as biomarkers in liver diseases

“…To the best of our knowledge, the presented work is the first study investigating EVs in patients with chronic liver diseases, and it supports the conclusion that analysis of EVs in crude serum might provide prognostic or diagnostic information. In this regard, we have recently shown that EVs sizes represent a novel prognostic marker in patients receiving transarterial chemoembolization (TACE) for primary and secondary hepatic malignancies [38].…”