| Liquid biopsy may play an important role for aiming at precision medicine in HCC, where tumor biopsy tends to be avoided due to the risk of dissemination. Here, we conducted a pilot study to investigate the usefulness of liquid biopsy using plasma-derived cell-free DNA (cfDNA) from 70 HCC patients. The concentration of circulating cfDNA (ng/mL) increased according to BCLC stage as follows; A: 39.4 (26.7-55.0, n=38); B: 48.7 (33.6-80.1, n=21); C: 94.6 (51.8-183.3, n=11). TERT C228T or C250T mutation was detected in 38 out of the 70 HCCs (54%) using droplet digital PCR. The presence of TERT promoter mutations was associated with elevated tumor markers; in particular, L3-AFP was significantly higher in HCC with TERT promoter mutations (3.2% vs 11.3%. p = 0.04). The concentration of cfDNA was significantly increased after a few days from treatment; from 39.6 to 99.4 in RFA (p < 0.01, n=31), from 51.3 to 161.6 in TACE (p = 0.03, n=16), and from 50.0 to 77.6 in TKI (p= 0.02, n=15). There were several cases in which TERT promoter mutations were detected only from post-treatment-cfDNA, suggesting that circulating tumor DNA (ctDNA) might be enriched after several days from treatment. Gene mutation analysis using cfDNA collected in large amounts after treatment may be a useful strategy for further precision medicine in HCC treatment. |
