Author：Zhen Li, Xiao Du, Linlin Yan, Xin Li, Xinwei Han, Henghui Zhang
Background: Hepatocellular carcinoma (HCC) is one of the most common prevalent fatal cancers worldwide with poor prognosis due to high incidence of recurrence. For patients with advanced HCC, transcatheter arterial chemoembolization (TACE), a minimal invasive clinical nonsurgical treatment is the standard first-line option. However, current surveillance approaches based on serological examination (including AFP) and imaging (ultrasound, CT, MRI, etc.) are limited in early detection of residual cancer and relapse that result in the bottleneck of long-term effects after TACE therapy.
Methods: This study consists of two parts. In the first part, forty-one patients with HCC were included. According to number of tumor lesions, patients were classified into two groups: single lesion group (S) and multiple lesions group (M). In the second part, three patients with advanced HCC treated with TACE were included. Periodic evaluation of plasma cfDNA together with radiologic examination, laboratory testing (including AFP) were performed simultaneously to trace the dynamic response of HCC patients after TACE treatment. Tumor tissue DNA and matching cell-free DNA are subjected to enrichment for a 1.15M size panel covering exon regions of 1,086 genes. With next generation sequencing on an Illumina X10 platform, the captured sequencing data was further processed using bioinformatics analysis to identify somatic mutations, including single nucleotide variants (SNV), short insertions/deletions (indels) and copy number variations (CNVs).
Result: We showed that the mutational profiles of plasma cfDNA is in consistency with that of tumor tissue DNA. Using the mutation burden of 7 genes (CTNNB1, PIK3CA, MET, EGFR, FBXMW7, TP53, and ERBB2.), the M group can be distinguished from S group. In addition, plasma cfDNA mutation burden of 10 genes (NRAS, BRAF, PIK3CA, KRAS, ARID1A, AXIN1, ARID2, TERT, TP53, CTNNB1) indicates relapse weeks prior to conventional computed tomography (CT) imaging and Alpha-Fetoprotein (AFP) changes.
Conclusion: Our results suggest that plasma cfDNA serves as a promising surveillance tool of HCC patients treated with TACE. The high mutation burden status of 10 genes (NRAS, BRAF, PIK3CA, KRAS, ARID1A, AXIN1, ARID2, TERT, TP53, CTNNB1) might correlate with recurrence in HCC patients.