Transcriptome analysis of hepatocellular carcinoma and non-tumor region derived from patients with Fontan associated liver disease

To investigate the characteristics of hepatocellular carcinoma (HCC) and liver injury that occur in Fontan associated liver disease (FALD) patients, we performed whole transcriptome analysis and compared them with those of other etiologies in TCGA-LIHC database.
ESTIMATE was used to compare the immune cell infiltration and fibrotic components in tumor and non-tumor regions. Immune and stromal scores were high in 3 of 5 FALD HCC cases and 1 of 2 cases of HCC after the other congenital heart surgery, suggesting that immune cell infiltration differs from case to case. While there was no difference in stromal score among the groups in the noncancerous areas, the immune score was significantly higher in HCV related HCC than other etiologies. Gene set enrichment analysis showed that hepatocyte metabolic enzymes were negatively enriched in FALD HCC, reflecting the poor differentiated HCC, and VEGFA pathway, EGFR tyrosine kinase inhibitor resistance were enriched. Of note, the expression of TGFA, VEGFA, FGFR3 were significantly higher in FALD HCC than other etiologies. On the other hand, in non-tumor region, hepatocyte metabolic enzymes, especially carbohydrate metabolism, were enriched, while T cell-related gene sets were negatively enriched.
This analysis is useful for therapeutic strategies, especially tyrosine kinase inhibitors and immune checkpoint inhibitors and pathophysiological understanding of FALD and FALD HCC.