Division of Hepatobiliary Surgery, the First Affiliated Hospital of Guangxi Medical University, NO 6 Shuangyong Road, Nanning, Guangxi, 530021, China.
Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Guangxi Medical University, Ministry of Education, Nanning, Guangxi, 530021, China.
BMC Genomics. 2023 Sep 7;24(1):532. doi: 10.1186/s12864-023-09647-0.
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 death. Partial hepatectomy (pHx) and eHx mouse models were constructed, liver tissues were sampled at 18, 36, and 72 h posthepatectomy. Transcriptome and metabolome analyses were employed to explore the different potential mechanisms in regeneration and injury between pHx and eHx. The results showed that eHx was associated with more severe liver injury and lower survival rates than pHx. 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 posthepatectomy, respectively, compared with the those in the sham groups. Compared with pHx, the number of DEGs in the eHx group reached a maximum of 230 at 18 h after surgery and decreased sequentially to 87 and 43 at 36 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 for liver regeneration and mouse survival postextended hepatectomy. Our results showed the global influence of pHx and eHx on the transcriptome and metabolome in mouse liver, and revealed cholesterol metabolism and insulin resistance pathways might be involved in regeneration post-pHx and -eHx.
手术切除仍然是许多原发性和继发性肝肿瘤患者的重要治疗选择。对于一些肿瘤较大的患者，可能需要进行扩大肝切除术（eHx），这可能导致肝功能衰竭和死亡。构建了部分肝切除术（pHx）和 eHx 小鼠模型，在肝切除术后 18、36 和 72 小时采集肝组织样本。采用转录组和代谢组学分析方法，探讨 pHx 和 eHx 之间再生和损伤的不同潜在机制。结果表明，eHx 与 pHx 相比，肝损伤更严重，存活率更低。转录组学数据显示，eHx 在肝切除术后 18、36 和 72 小时分别有 1842、2129 和 1277 个差异表达基因（DEGs），pHx 分别有 962、1305 和 732 个 DEGs，与假手术组相比。与 pHx 相比，eHx 组的 DEG 数量在术后 18 小时达到最大值 230，随后依次减少至 36 小时的 87 和 72 小时的 43。代谢组学分析共鉴定出 1399 种代谢物，筛选出 eHx 和 pHx 之间 48 种显著差异产生的代谢物（DPM）。DEG 和 DPM 的联合分析表明，胆固醇代谢和胰岛素抵抗可能是肝再生和延长肝切除术后小鼠存活的两个重要途径。我们的研究结果表明 pHx 和 eHx 对小鼠肝转录组和代谢组的全局影响，并揭示胆固醇代谢和胰岛素抵抗途径可能参与 pHx 和 eHx 后的再生。
