代谢途径对癌症的发生和进展具有重大影响。肝细胞癌 (HCC) 患者的公共数据来自癌症基因组图谱 (TCGA) 和国际癌症基因组联盟 (ICGC) 数据库。使用不同的 R 包在 R 软件中进行分析。在这里，我们整合了多个独立 HCC 队列的数据，包括 TCGA-LIHC、ICGC-FR 和 ICGC-JP。然后，使用 ssGSEA 算法对 21 条代谢相关途径的富集得分进行量化。接下来，应用单变量 Cox 回归分析来识别与患者生存率显着相关的代谢项。最后，建立了基于亚油酸代谢、鞘脂代谢和脂肪细胞脂解调节的预后模型，在预测患者生存方面表现出良好的性能。此外，我们进行了生物富集分析，以描绘高风险和低风险患者之间的生物差异。值得注意的是，我们发现这两个患者组之间的微环境存在差异。我们还发现低风险患者可能对免疫疗法有更好的反应。药物敏感性分析表明，低风险患者对贝沙罗汀和厄洛替尼更敏感，但对 ATRA 和博莱霉素表现出耐药性。此外，通过使用LASSO逻辑回归分析，我们确定了19个特征基因，可以稳健地指示风险群体。我们的研究强调了亚油酸代谢、鞘脂代谢和脂肪细胞脂肪分解调节在 HCC 中的作用，为未来研究指明了潜在途径。© 2023 作者。细胞与分子医学基金会和约翰·威利出版的《细胞与分子医学杂志》

Metabolic pathways exert a significant influence on the onset and progression of cancer. Public data on hepatocellular carcinoma (HCC) patients were obtained from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases. Analysis was performed in R software using different R packages. Here, we integrated the data from multiple independent HCC cohorts, including TCGA-LIHC, ICGC-FR and ICGC-JP. Then, the enrichment score of 21 metabolism-related pathways was quantified using the ssGSEA algorithm. Next, univariate Cox regression analysis was applied to identify the metabolic terms with significant correlation to patient survival. Finally, a prognosis model based on linoleic acid metabolism, sphingolipid metabolism and regulation of lipolysis in adipocytes was established, which showed good performance in predicting patients' survival. Furthermore, we conducted a biological enrichment analysis to delineate the biological disparities between high- and low-risk patients. Notably, we discerned differences in the microenvironments between these two patient groups. We also found that low-risk patients could potentially respond better to immunotherapy. Drug sensitivity analysis suggested that low-risk patients are more susceptible to bexarotene and erlotinib, yet exhibit resistance to ATRA and bleomycin. Furthermore, through the use of LASSO logistic regression analysis, we identified 19 characteristic genes, which could robustly indicate the risk groups. Our research underscores the role of linoleic acid metabolism, sphingolipid metabolism and the regulation of lipolysis in adipocytes in HCC, pointing towards potential avenues for future research.© 2023 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.