早期食管癌的综合蛋白质基因组学特征分析。
Integrative proteogenomic characterization of early esophageal cancer.
机构信息
State Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Institute of Biomedical Sciences, Human Phenome Institute, Zhongshan Hospital, Fudan University, Shanghai, 200433, China.
Department of Pathology, Zhongshan Hospital Fudan University, Shanghai, 200032, China.
出版信息
Nat Commun. 2023 Mar 25;14(1):1666. doi: 10.1038/s41467-023-37440-w.
Esophageal squamous cell carcinoma (ESCC) is malignant while the carcinogenesis is still unclear. Here, we perform a comprehensive multi-omics analysis of 786 trace-tumor-samples from 154 ESCC patients, covering 9 histopathological stages and 3 phases. Proteogenomics elucidates cancer-driving waves in ESCC progression, and reveals the molecular characterization of alcohol drinking habit associated signatures. We discover chromosome 3q gain functions in the transmit from nontumor to intraepithelial neoplasia phases, and find TP53 mutation enhances DNA replication in intraepithelial neoplasia phase. The mutations of AKAP9 and MCAF1 upregulate glycolysis and Wnt signaling, respectively, in advanced-stage ESCC phase. Six major tracks related to different clinical features during ESCC progression are identified, which is validated by an independent cohort with another 256 samples. Hyperphosphorylated phosphoglycerate kinase 1 (PGK1, S203) is considered as a drug target in ESCC progression. This study provides insight into the understanding of ESCC molecular mechanism and the development of therapeutic targets.
食管鳞状细胞癌（ESCC）是恶性的，但其致癌机制尚不清楚。在这里，我们对 154 名 ESCC 患者的 786 个微量肿瘤样本进行了全面的多组学分析，涵盖了 9 个组织病理学阶段和 3 个阶段。蛋白质基因组学阐明了 ESCC 进展中的癌症驱动波，并揭示了与饮酒习惯相关特征的分子特征。我们发现 3q 染色体增益在从非肿瘤到上皮内瘤变阶段的传递中起作用，并发现 TP53 突变增强了上皮内瘤变阶段的 DNA 复制。AKAP9 和 MCAF1 的突变分别在上皮内瘤变阶段上调糖酵解和 Wnt 信号通路。在 ESCC 进展过程中与不同临床特征相关的六个主要轨迹被确定，这在另一个包含 256 个样本的独立队列中得到了验证。高度磷酸化的磷酸甘油酸激酶 1（PGK1，S203）被认为是 ESCC 进展中的一个药物靶点。这项研究为理解 ESCC 的分子机制和治疗靶点的发展提供了新的见解。
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