在美国，西班牙裔人的肝细胞癌（HCC）发病率和死亡率远高于非西班牙裔白人。我们进行了多组学分析，以阐明西班牙裔患者 HCC 的分子变化。从德克萨斯州南部的 31 个西班牙裔 HCC (STX-Hispanic) 中收集了配对肿瘤和邻近非肿瘤样本，进行基因组、转录组、蛋白质组和代谢组学分析。对 40 名患有或不患有临床诊断的 HCC 的西班牙裔和非西班牙裔患者的血清脂质进行了分析。外显子组测序显示，STX 西班牙裔 HCC 中 AXIN2 和 CTNNB1 的突变频率较高，表明 Wnt/β-catenin 通路的主要激活。 TERT 启动子突变在西班牙裔人群中也显着更频繁（Fisher 精确检验，p< .05）。通过基因集富集分析，细胞周期和肝功能分别得到正向富集和负向富集。代表特定肝脏代谢途径的基因集与相应代谢物的失调相关。肝脏脂肪生成和脂质代谢的负富集证实了 HCC 患者血清样本中大多数脂质的显着降低（配对 t 检验，p< .0001）。我们的西班牙裔队列中的两种 HCC 亚型通过 TCGA 肝癌队列进行了鉴定和验证。总体生存率较高的患者表现出较高的免疫和血管生成特征活性，以及​​较低的肝功能相关基因特征活性。他们的免疫检查点和免疫耗竭标记物水平也较高。我们的研究揭示了西班牙裔 HCC 的特定分子特征和治疗管理的潜在生物标记物。它为研究西班牙裔 HCC 提供了独特的资源。© 作者 2024。由牛津大学出版社出版。版权所有。如需权限，请发送电子邮件至：journals.permissions@oup.com。

The incidence and mortality rates of hepatocellular carcinoma (HCC) among Hispanic individuals in the United States are much higher than in non-Hispanic white people. We conducted multi-omics analyses to elucidate molecular alterations in HCC among Hispanic patients.Paired tumor and adjacent non-tumor samples were collected from 31 Hispanic HCCs in South Texas (STX-Hispanic) for genomic, transcriptomic, proteomic, and metabolomic profiling. Serum lipids were profiled in 40 Hispanic and non-Hispanic patients with or without clinically diagnosed HCC.Exome sequencing revealed high mutation frequencies of AXIN2 and CTNNB1 in STX Hispanic HCCs, suggesting a predominant activation of the Wnt/β-catenin pathway. TERT promoter mutations were also significantly more frequent in the Hispanic cohort (Fisher's exact test, p < .05). Cell cycles and liver function were positively and negatively enriched, respectively, with gene set enrichment analysis. Gene sets representing specific liver metabolic pathways were associated with dysregulation of corresponding metabolites. Negative enrichment of liver adipogenesis and lipid metabolism corroborated with a significant reduction in most lipids in serum samples of HCC patients (paired t-test, p < .0001). Two HCC subtypes from our Hispanic cohort were identified and validated with the TCGA liver cancer cohort. Patients with better overall survival showed higher activity of immune and angiogenesis signatures, and lower activity of liver function-related gene signatures. They also had higher levels of immune checkpoint and immune exhaustion markers.Our study revealed specific molecular features of Hispanic HCC and potential biomarkers for therapeutic management. It provides a unique resource for studying Hispanic HCC.© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.