Cong Shan, Bai Shanshan, Bi Yanfang, Wang Yu, Jin Shi, He Hui
Department of Laparoscopic Surgery, The First Affiliated Hospital of Dalian Medical University Dalian 116000, Liaoning, China.
Department of Ultrasound, The First Affiliated Hospital of Dalian Medical University Dalian 116000, Liaoning, China.
Am J Cancer Res. 2023 Jul 15;13(7):2814-2840. eCollection 2023.
Consensus on the stage of liver hepatocellular carcinoma (LIHC) in patients is difficult, which restricts the diagnosis and treatment of liver cancer. Molecular typing based on genes related to the lipid metabolism pathways can reflect deeper characteristics of liver cancer and complement the deficiency of the clinical staging system. In this study, we constructed and verified two cell subtypes: C1 and C2 in LIHC, based on six lipid metabolic pathway-associated genes identified in two independent external validation cohorts comprising single-cell RNA-sequencing technology (scRNA-Seq) data and bulk RNA-seq data downloaded from Gene Expression Omnibus (GEO) database and The Cancer Genome Atlas (TCGA) database. The C2 subtype showed poorer prognosis, higher immune scores, and greater correlation with pathways associated with tumor progression as compared to the C1 subtype. Moreover, the sensitivity of many tested targeted drugs in C1 was relative to C2. Furthermore, Gene Set Enrichment Analysis (GSEA) revealed several significantly enriched oncological signatures and metabolic processes, which might help elucidate the underlying molecular mechanisms. At the same time, we identified there were significantly different metabolites in C1 and C2 subtypes using 11 LIHC tissue samples. In conclusion, we constructed two molecular subtypes based on the lipid metabolism-associated genes, which may provide valuable information to further study the pathogenesis and devise clinical management strategies for LIHC.
肝癌患者肝癌分期的共识难以达成，这限制了肝癌的诊断和治疗。基于脂质代谢途径相关基因的分子分型能够反映肝癌更深层次的特征，并弥补临床分期系统的不足。在本研究中，我们基于从基因表达综合数据库（GEO）和癌症基因组图谱（TCGA）数据库下载的单细胞RNA测序技术（scRNA-Seq）数据和批量RNA测序数据的两个独立外部验证队列中鉴定出的六个脂质代谢途径相关基因，构建并验证了肝癌中的两种细胞亚型：C1和C2。与C1亚型相比，C2亚型预后较差、免疫评分较高，且与肿瘤进展相关途径的相关性更强。此外，许多测试的靶向药物在C1中的敏感性相对于C2更高。此外，基因集富集分析（GSEA）揭示了几个显著富集的肿瘤学特征和代谢过程，这可能有助于阐明潜在的分子机制。同时，我们使用11个肝癌组织样本鉴定出C1和C2亚型中存在显著不同的代谢物。总之，我们基于脂质代谢相关基因构建了两种分子亚型，这可能为进一步研究肝癌的发病机制和制定临床管理策略提供有价值的信息。
