Basic and translational research in hepatoblastoma

Abstract

To improve the survival rate in hepatoblastoma (HB), novel prognostic markers and therapeutic targets should be identified. Altered DNA methylation patterns are biologically and clinically important in HB. We evaluated the methylation status of RASSF1A, MST1R, OCIAD2, and PARP6, whose hypermethylation was associated with several clinicopathological characteristics in 132 patients with HB, using bisulfite pyrosequencing analysis. Hypermethylation in ≥2 of the four genes was significantly associated with poorer OS and EFS. Multivariate analysis indicated that ≥2 methylated genes was an independent prognostic factor. Moreover, it was associated with poorer OS in the CHIC-very low (VL)-/low (L)-risk group and CHIC-intermediate (I) risk group (3-year OS rates; 83% vs. 98% and 50% vs. 95%, respectively). The 3-year OS rates of the VL/L, I, and high-risk groups in the new stratification model (methylation-based CHIC-HS; mCHIC-HS) were 98%, 90%, and 63% (vs. CHIC-HS [96%, 82%, and 66%, respectively]), optimizing CHIC-HS. The proposed stratification system may improve the clinical management of HB according to individual risk in patients with HB.