Serum microparticles (MPs) as a novel tool to predict hepatocellular carcinoma (HCC) and tumor size
Background and aims: We recently showed that subpopulations of serum/plasma microparticles (MPs) serve as novel diagnostic tools to stage and grade chronic hepatitis C (CHC) and nonalcoholic steatohepatitis (NASH) (Kornek M et al., Hepatology 2011; Gastroenterology 2012). Here, we studied if circulating MPs may help to identify patients with HCC or who are at risk of developing HCC. We therefore performed a pilot study to test if and how far HCC-associated MPs permit to predict the presence and size of HCCs in a cohort of patients with CHC with or without HCC in a blinded approach.
Methods: MPs were isolated from human serum samples of patients with CHC and cirrhosis (n = 35), 17 of them with histologically proven HCC, without knowing their HCC status. Sera from twelve healthy patients served as normal controls. MP profiling was done after differential ultracentrifugation using FACS analysis for the presence and quantity of CD133+ MPs and HCC derived MPs.
Results: Proven HCC was associated with a marked increase of CD133+ and HCC derived MPs which successfully separated CHC patients without HCC from those with HCC and from healthy controls. Hepatocyte (ASGPR1) and EpCAM+ cell derived MPs were non-significantly elevated or remained unchanged. The calculated cut-off values were 2.4% for CD133+ MPs and 0.11% for HCC derived MPs. HCC derived MPs were increased 2-fold (p < 0.005) in HCC patients compared to HCC negative CHC patients. CD133+ MPs were significantly increased by 1.5 fold (p < 0.05) in HCC positive vs. HCC negative CHC samples. Their AUROC values, sensitivity and specificity scores indicated a high diagnostic accuracy (CD133+ MPs: AUROC 0.84, sensitivity: 71.4%, specificity: 94.4%; HCC MPs: AUROC 0.83, sensitivity: 71.4%, specificity: 85.7%). Moreover, HCC derived MPs correlated significantly (r = 0.5003, p < 0.05) with HCC tumor volume.
Conclusions: 1. Patients with HCC were characterized by a striking elevation of CD133+ and HCC derived MPs. 2. MP monitoring for HCC is a novel tool to noninvasively assess the presence and possibly the tumor volume of HCC.
Studies were supported by a DFG – fellowship (KO 4103/1 – 1) to MK and grant R21 DK075857 – 01A2 to DS