Zhang Wenda, Zhou Xinyi, Lin Lili, Lin Anqi, Cheng Quan, Liu Zaoqu, Luo Peng, Zhang Jian
Department of Oncology, Zhujiang Hospital of Southern Medical University, Guangzhou, China.
Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, China.
Heliyon. 2024 Sep 2;10(17):e37327. doi: 10.1016/j.heliyon.2024.e37327. eCollection 2024 Sep 15.
The heterogeneity of immune cells and metabolic pathways in hepatocellular carcinoma (HCC) patients has not been fully elucidated, leading to diverse clinical outcomes. Accurately distinguishing different HCC subtypes and recommending appropriate treatments is are highly important. In this study, we conducted a comprehensive analysis of 28 immune cells and 85 metabolic pathways in the TCGA-LIHC and GSE14520 datasets. Metabolism-related first principal component (MRPC1) and cytotoxic T lymphocyte (CTL) infiltration were used to assess the metabolic and immune infiltration levels of HCC patients, respectively. These two quantifiable indicators were then used to construct an immune‒metabolic classifier, which categorized HCC patients into three distinct groups. The potential biological mechanisms were explored through multiomics analysis, revealing that group S1 exhibited high metabolic activity and a high level of immune infiltration, that group S2 presented a low level of immune infiltration, and that group S3 presented low metabolic activity. This new immune‒metabolic classifier was well validated in a pancancer cohort of 9296 patients. The efficacy of multiple treatment approaches was assessed in relation to different immune‒metabolic groups, indicating that group S1 patients may benefit from immunotherapy, that group S2 patients are suitable for transcatheter arterial chemoembolization (TACE), and that group S3 patients are appropriate candidates for tyrosine kinase inhibitors. In conclusion, this immune‒metabolic classifier is anticipated to address the differences in treatment efficacy among HCC patients due to the heterogeneity of the tumor microenvironment, and to help refine the individualized treatment choices for clinical patients.
肝细胞癌（HCC）患者免疫细胞和代谢途径的异质性尚未完全阐明，导致了多样的临床结果。准确区分不同的HCC亚型并推荐合适的治疗方法非常重要。在本研究中，我们对TCGA-LIHC和GSE14520数据集中的28种免疫细胞和85条代谢途径进行了综合分析。代谢相关第一主成分（MRPC1）和细胞毒性T淋巴细胞（CTL）浸润分别用于评估HCC患者的代谢和免疫浸润水平。然后，利用这两个可量化指标构建了一个免疫代谢分类器，将HCC患者分为三个不同的组。通过多组学分析探索了潜在的生物学机制，结果显示S1组具有高代谢活性和高水平的免疫浸润，S2组免疫浸润水平低，S3组代谢活性低。这个新的免疫代谢分类器在一个包含9296名患者的泛癌队列中得到了很好的验证。评估了多种治疗方法针对不同免疫代谢组的疗效，表明S1组患者可能从免疫治疗中获益，S2组患者适合经动脉化疗栓塞术（TACE），S3组患者是酪氨酸激酶抑制剂的合适候选者。总之，预计这个免疫代谢分类器能够解决由于肿瘤微环境异质性导致的HCC患者治疗疗效差异问题，并有助于优化临床患者的个体化治疗选择。
