Effect of Pre-operative Trans-Arterial Embolisation (TAE) on Circulating Tumor Cells and Recurrence in Hepatocellular Carcinoma

Purpose: Hepatocellular carcinoma is the most common primary liver malignancy and is the third leading cause of cancer death. Circulating Tumor Cells are a promising marker to monitor the progression of HCC. CTC dissemination during the operative procedure can lead to disease recurrence. The effect of preoperative Transarterial Embolization on release of CTCs and miRNA panels in recurrence and progression of HCC has been evaluated in this study. Materials and Methods: The study included non-metastatic HCC >5cm in size which was completely resected using TAE (n=10). Blood was collected pre-TAE, post-TAE, post-operative (day 2,30 and 180) and analyzed for the presence of CTC and miRNA (miR885-5p, miR22-3p, miR 642b-5p). The samples were subjected CTC enrichment, isolation and staining using the markers CD45, EpCAM and Cytokeratin (CK). The data was analyzed using Gene Expression Suite software. Results: The CTC enumeration resulted in three groups: Group 1- CTC present at both Pre TAE and post-operative day 30 (n=4), Group 2- CTC present at Pre TAE and clearing at post-operative day 30 (n=2), Group 3- No CTC detected at any stages (n=3). Group 2 patients had better survival as compared to the other groups. miR885-5p downregulated in all the three groups. miR22-3p downregulation was associated with the poor survival outcomes in Group 1 whereas upregulation was associated with better survival outcomes in group 2 and 3. A larger study to evaluate the significance of CTCs as a prognostic marker is warranted to further evaluate these findings. Conclusion: While preoperative TAE may not provide much benefit, the use of CTCs and miRNA 22-3p may provide important prognostic information in patients undergoing curative liver resections for HCC. A larger randomized study is needed to determine whether additional adjuvant therapy improved outcomes in patients with persistent CTC on POD 30 or down-regulated miRNA 22-3p.