Distinct clinical and genetic characteristics of AFP-negative hepatocellular carcinoma patients infected by HBV or HCV.

Abstract

e16620 Background: The serum level of alpha-fetoprotein (AFP) is a key biomarker in hepatocellular carcinoma (HCC) screening regardless of the high false-negative rates. Studies have characterized AFP negative HCC patients, however, the differences between HBV and HCV infected AFP negative HCC patients have not been discussed. Methods: The clinical profiles and whole-exome sequencing data of 243 patients were downloaded from the TCGA database. Patients were divided into 4 groups based on their virus infection status and serum AFP measurements as indicated in the table. The mutation profiles and clinical features of the patients were analyzed. Results: In the HBV infected groups, the AFP+ patients carried significantly larger tumors (n = 17, 85.88±11.87 mm) compared to the AFP- patients (n = 13, 49.08±8.933 mm, p = 0.026). The HBV+ AFP+ group exhibited the prevalence of vascular invasion (VI, 76%, 13/17) while less than half of the patients in the HBV+ AFP- group developed VI (46%, 6/13). The WES results identified shared mutations in more than 10% of patients in each group. It appeared that 126 shared mutations were restricted to the HBV+ AFP+ group, they are involved in the regulation of ion transmembrane transport (p < 0.001) and interaction between L1 and Ankyrins (p < 0.0001). Only 51 shared mutations were exclusive to the HBV+ AFP- group, they majorly affect developmental growth (p < 0.001) and skeletal system development (p < 0.01). In contrast, the tumor sizes of HCV+ AFP+ and HCV+ AFP- patients are similar (55.18±7.781 vs 48.19±5.564, p = 0.47), while the VI rate is higher in the HCV+ AFP- group (63%, 17/29, Table). In total, 11 shared mutations were restricted to the HCV+ AFP+ group, several of the genes were involved in the generation of precursor metabolites and energy (p < 0.01) and activation of immune response (p < 0.01). 27 shared mutations were exclusive to the HCV+ AFP- group, the enrichment analysis showed that they are related to the regulation of synapse organization (p < 0.0001) and the regulation of chromosome organization (p < 0.01). Conclusions: HBV and HCV infection were associated with distinct clinical features among the AFP positive and AFP negative patients. The differences were underpinned by the mutations exclusive to each group, and they were involved in distinct molecular and cellular functions. [Table: see text]