Abstract
Hepatocellular carcinoma (HCC) is a highly vascular tumor through the process of angiogenesis. To evaluate more non-invasive techniques for assessment of blood flow (BF) in HCC, this study examined the relationships between BF of HCC measured by computer tomography (CT) perfusion imaging and four circulating angiogenic factors in HCC patients. Interleukin 6 (IL-6), interleukin 8 (IL-8), vascular endothelial growth factor (VEGF), and platelet derived growth factor (PDGF) in plasma were measured using Bio-Plex multiplex immunoassay in 21 HCC patients and eight healthy controls. Circulating IL-6, IL-8 and VEGF showed higher concentrations in HCC patients than in controls (p < 0.05), and predicted HCC occurrence better than chance (p < 0.01). Twenty-one patients with HCC received 21-phase liver imaging using a 64-slice CT. Total BF, arterial BF, portal BF, arterial fraction (arterial BF/total BF) of the HCC and surrounding liver parenchyma, and HCC-parenchyma ratio were measured using a dual-vessel model. After analyzing the correlations between BF in HCC and four circulating angiogenic factors, we found that the HCC-parenchyma ratio of arterial BF showed a significantly positive correlation with the level of circulating IL-8 (p < 0.05). This circulating biomarker, IL-8, provides a non-invasive tool for assessment of BF in HCC.
Highlights
Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related death worldwide with six million new cases diagnosed annually [1]
Quantification of HCC angiogenesis has been studied with magnetic resonance imaging (MRI) and computed tomography (CT) perfusion imaging, contrast ultrasound, Doppler ultrasound, microvessel density (MVD), and circulating biomarkers to correlate with the patient’s prognosis and response to therapy [5,6,7,8]
Circulating Interleukin 6 (IL-6), interleukin 8 (IL-8), and vascular endothelial growth factor (VEGF) were significantly higher in 21 HCC patients than eight healthy controls, (p < 0.05) (Figure 1A–C) but the platelet derived growth factor (PDGF) did not significantly differ between these two groups (Figure 1D)
Summary
Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related death worldwide with six million new cases diagnosed annually [1]. Quantification of HCC angiogenesis has been studied with magnetic resonance imaging (MRI) and computed tomography (CT) perfusion imaging, contrast ultrasound, Doppler ultrasound, microvessel density (MVD), and circulating biomarkers to correlate with the patient’s prognosis and response to therapy [5,6,7,8]. To find convenient and quantitative parameters to evaluate BF of HCC in this study, we detected multiple circulating angiogenic factors by using a multiplex immunoassay technique and analyzed the BF of HCC performed by 64-slice CT perfusion imaging and commercial imaging software. We compared the perfusion parameters between non-tumor liver parenchyma and HCC using a dedicated CT perfusion imaging with dual vascular data.
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