根据格里森三联征的分布，肝脏在解剖学上分为八个部分。然而，每个片段的分子机制及其与肝细胞癌（HCC）异质性的关联尚不清楚。在本研究中，我们的目标是对分割图谱进行全面的多组学分析，以研究 HCC 的潜在亚型和治疗方法。采用高通量液相色谱-串联质谱仪策略来全面分析蛋白质组、脂质组和代谢组数据，重点是分段解析的多组学分析。为了对 HCC 亚型进行分类，将获得的数据与正常参考分析进行整合。此外，使用免疫组织化学测定确定了 HCC 的潜在治疗靶点。这些靶标的有效性通过患者来源的类器官 (PDO) 检测得到进一步验证。对 8536 个高置信度蛋白质、1029 个极性代谢物和 3381 个非冗余脂质进行多组学分析，以分析 HCC 的分割图谱。数据分析显示，在正常邻近组织中，左叶主要参与能量代谢，而右叶则与小分子代谢相关。根据正常参考图谱，将HCC患者进行节段分辨分类分为三个亚型。 C1亚型在核糖体生物发生方面表现出富集，C2亚型表现出中间表型，而C3亚型与中性粒细胞脱颗粒密切相关。此外，使用 PDO 测定，输出蛋白 1 (XPO1) 和 5-脂氧合酶 (ALOX5) 分别被确定为 C1 和 C3 亚型的潜在靶标。我们对多组学分析中的分段图谱进行了广泛分析，定义了 HCC 的分子亚型并揭示了有可能增强 HCC 预后的潜在治疗策略。© 2024 作者。约翰·威利出版的《临床与转化医学》

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.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.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 ribosome biogenesis, the C2 subtype exhibited an intermediate phenotype, while the C3 subtype was closely associated with neutrophil degranulation. Furthermore, using the PDO assay, exportin 1 (XPO1) and 5-lipoxygenase (ALOX5) were identified as potential targets for the C1 and C3 subtypes, respectively.Our extensive analysis of the segmentation atlas in multiomics profiling defines molecular subtypes of HCC and uncovers potential therapeutic strategies that have the potential to enhance the prognosis of HCC.© 2024 The Author(s). Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.