Abstract 521: Dynamic measurements of circulating microRNAs reflect different biological effects of radiofrequency ablation and transarterial chemoembolisation in liver cancer patients
Authors: Juracek Jaroslav , Andrasina Tomas , Cechova Barbora , Vesela Petra , Zavadil Jan , Machackova Tana , Sana Jiri , Vecera Marek , Gablo Natalia , Svoboda Marek , Goldberg Nahum , Slaby Ondrej 
Published: August 2018

Abstract
Introduction: The majority of primary or metastatic liver tumors are unresectable (because of tumor size, location, poor performance status or multifocality), therefore other therapeutic modalities as radiofrequency ablation (RFA) and transarterial chemoembolization (TACE) are applied. RFA is a localized thermal treatment technique designed to produce tumor destruction by heating tumor tissue, while TACE combines cytotoxic effect of particle based tumor ischemia and locoregional chemotherapy. Both methods cause characteristic changes in liver tissue (inflammation, hypoxia, elevated temperature, tissue destruction) accompanied by targeted systemic secretion of microRNA into the bloodstream. Since RFA and TACE differ in the dynamics with which they affects the tumor tissue, we aimed to investigate whether the expression level of circulating microRNAs related to hypoxia (miR-21 and miR-210), liver injury (miR-122) and epithelial-mesenchymal transition (miR-200a) could reflect such changes.
Material and methods: This study consisted of 14 patients diagnosed with primary hepatocellular carcinoma (HCC) (median age 73; TACE) and 20 patients diagnosed with liver metastases of colorectal cancer (median age 63; 17 patients - RFA, 3 patients - TACE). RFA was performed using the rf/mw generator (AngioDynamics). For TACE drug eluting beads (Biocompatibles Ltd.) loaded with irinotecan for mCRC patients and doxorubicin for HCC patients were used. The concentrations of miRNA were determined for all patients in series of blood plasma from 4 time points (before intervention, immediately after intervention, 24 hours after intervention, 1 week after intervention) using miRNA-specific TaqMan assays and qRT-PCR method.
Results: In RFA cases we observed significant increase of investigated miRNA concentrations immediately after intervention (miR-122, FC = 15, P = 0.0002; miR-200a, FC = 1.9, P = 0.015). In TACE we observed delayed increase in circulating miRNA concentrations at time point 24 hours after intervention (miR-21, FC = 10.4, P &lt; 0.0001; miR-210, FC = 9.0, P = 0.03; miR-122, FC = 27, P = 0.0004; miR-200a, FC = 4.0, P = 0.0098). In both methods, the initial increase was followed by a steady decline of miRNA levels. Identified dynamic changes in circulating miRNA levels were in accordance with the nature of RFA and TACE biologic effects. In selected cases, we observed specific dynamic miRNA patterns to be linked to the course of the disease (e.g. necessity of additional intervention).
Conclusions: Our preliminary data indicates potential usage of circulating miRNAs for monitoring of the systemic effects of RFA and TACE therapy and their ability to reflect efficacy of intervention procedures. This work was supported by Ministry of Health of the Czech Republic, grant nr. 15-33158A, 15-34553A, 15-31627A, 16-31314A, and 15-34678A.
Citation Format: Jaroslav Juracek, Tomas Andrasina, Barbora Cechova, Petra Vesela, Jan Zavadil, Tana Machackova, Jiri Sana, Marek Vecera, Natalia Gablo, Marek Svoboda, Nahum Goldberg, Ondrej Slaby. Dynamic measurements of circulating microRNAs reflect different biological effects of radiofrequency ablation and transarterial chemoembolisation in liver cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 521.