超重和肥胖的患病率不断增加，导致代谢相关脂肪肝病（MAFLD），其特征是肝脏脂肪过度积累，并有患肝细胞癌（HCC）的风险。驱动基因突变可能扮演发生在单一“热点”的过客角色，并能促进肿瘤从良性病变到恶性病变的发生。我们使用癌症基因组图谱肝癌 (TCGA-LIHC) 数据集研究了高体重和 BMI 对 HCC 生存的影响。为了探讨肥胖相关基因突变对 HCC 的影响，我们收集了 34 名 BMI ≥ 27 的 TCGA 患者和 23 名 BMI < 27 的 TCGA 患者的驱动突变基因。 96 名 NAFLD 患者。我们的分析表明，肥胖会导致 HCC 的生存结果显着恶化。使用 cbioportal，我们在肥胖患者中鉴定了 414 个驱动突变基因，在非肥胖患者中鉴定了 127 个驱动突变基因。功能分析表明，肥胖相关基因显着丰富了肝癌中调节脂质和胰岛素的通路。肥胖 HCC 特异性生存患者的胰岛素分泌途径将 ABCC8 和 PRKCB 确定为重要基因 (p<0.001)。它揭示了与非肥胖患者相比，基因突变和基因表达谱的显着差异。数字PCR检测在PBMC样本中检测到ABCC8变异，变异率为14.5%，显着高于非肥胖NAFLD患者。研究结果表明，基因ABCC8是NAFLD中肥胖相关基因的患者，这提供了ABCC8突变有助于HCC癌前病变生物标志物的可能性。© 2024。作者，独家许可施普林格自然出版社德国施普林格出版社。

The prevalence of overweight and obesity is increasing, leading to metabolic-associated fatty liver disease (MAFLD) characterized by excessive accumulation of liver fat and a risk of developing hepatocellular carcinoma (HCC). The driver gene mutations may play the roles of passengers that occur in single 'hotspots' and can promote tumorigenesis from benign to malignant lesions. We investigated the impact of high body weight and BMI on HCC survival using The Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC) dataset. To explore the effects of obesity-related gene mutations on HCC, we collected driver mutation genes in 34 TCGA patients with BMI ≥ 27 and 23 TCGA patients with BMI < 27. The digital PCR performing the PBMC samples for the variant rate by clinical cohort of 96 NAFLD patients. Our analysis showed that obesity leads to significantly worse survival outcomes in HCC. Using cbioportal, we identified 414 driver mutation genes in patients with obesity and 127 driver mutation genes in non-obese patients. Functional analysis showed that obese-related genes significantly enriched the regulated lipid and insulin pathways in HCC. The insulin secretion pathway in patients with obesity HCC-specific survival identified ABCC8 and PRKCB as significant genes (p < 0.001). It revealed significant differences in gene mutation and gene expression profiles compared to non-obese patients. The digital PCR test ABCC8 variants were detected in PBMC samples and caused a 14.5% variant rate, significantly higher than that of non-obese NAFLD patients. The study findings showed that the gene ABCC8 was a patient with the obesity-related gene in NAFLD, which provides the probability that ABCC8 mutation contributes to the pre-cancer lesion biomarker for HCC.© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.