Transcriptome sequencing and metabolome analysis reveal metabolic reprogramming of partial hepatectomy and extended hepatectomy

Abstract

Abstract Surgical resection remains a critical treatment option for many patients with primary and secondary hepatic neoplasms. Extended hepatectomy (eHx) may be required for some patients with large tumors, which may cause liver failure and individual death. Partial hepatectomy (pHx) and eHx mouse models were constructed, liver tissues were sampled at 18, 36, and 72 h post-hepatectomy, transcriptome and metabolome analyses were employed to find the differences in regeneration and injury between pHx and eHx. The results showed that eHx was associated with more severe liver injury and lower survival rates compared with pHx. Compared with the sham groups, transcriptomics data showed there were 1842, 2129, and 1277 differentially expressed genes (DEGs) in eHx and 962, 1305, and 732 DEGs in pHx at 18, 36, and 72 h post-hepatectomy, respectively. Compared with pHx, the number of DEGs reached a maximum of 230 at 18 h after surgery and decreased sequentially to 87 and 43 at 36 h and 72 h. Metabolomics analysis identified a total of 1399 metabolites, and 48 significant differentially produced metabolites (DPMs) were screened between eHx and pHx. Combined analysis of DEGs and DPMs indicated that cholesterol metabolism and insulin resistance may be two important pathways to liver regeneration and mouse survival post-extended hepatectomy. Our results showed the global influence of pHx and eHx on the transcriptome and metabolome in mouse liver, as both cholesterol metabolism and insulin resistance pathways were altered both at the transcriptional and metabolic levels between pHx and eHx groups.