Integrative multiomics analysis identifies molecular subtypes and potential targets of hepatocellular carcinoma

作者：Shuai Yang, Lu Zheng, Lingling Li, Jiangang Zhang, Jingchun Wang, Huakan Zhao, Yu Chen, Xudong Liu, Hui Gan, Junying Chen, Mei Yan, Chuanyin He, Kai Li, Chen Ding, Yongsheng Li · 发表于：Clinical and Translational Medicine · 年份：2024 · DOI：10.1002/ctm2.1727 · 被引用次数：14 · 研究领域：Metabolomics and Mass Spectrometry Studies、Ferroptosis and cancer prognosis、Hepatocellular Carcinoma Treatment and Prognosis

BACKGROUND: The liver is anatomically divided into eight segments based on the distribution of Glisson's triad. However, the molecular mechanisms underlying each segment and its association with hepatocellular carcinoma (HCC) heterogeneity are not well understood. In this study, our objective is to conduct a comprehensive multiomics profiling of the segmentation atlas in order to investigate potential subtypes and therapeutic approaches for HCC. METHODS: A high throughput liquid chromatography-tandem mass spectrometer strategy was employed to comprehensively analyse proteome, lipidome and metabolome data, with a focus on segment-resolved multiomics profiling. To classify HCC subtypes, the obtained data with normal reference profiling were integrated. Additionally, potential therapeutic targets for HCC were identified using immunohistochemistry assays. The effectiveness of these targets were further validated through patient-derived organoid (PDO) assays. RESULTS: A multiomics profiling of 8536 high-confidence proteins, 1029 polar metabolites and 3381 nonredundant lipids was performed to analyse the segmentation atlas of HCC. The analysis of the data revealed that in normal adjacent tissues, the left lobe was primarily involved in energy metabolism, while the right lobe was associated with small molecule metabolism. Based on the normal reference atlas, HCC patients with segment-resolved classification were divided into three subtypes. The C1 subtype showed enrichment in riboso...