Integrating Single-Cell and Spatial Transcriptomics to Uncover and Elucidate GP73-Mediated Pro-Angiogenic Regulatory Networks in Hepatocellular Carcinoma  

作　　者：Jiazhou Ye Xing Gao Xi Huang Shilin Huang Dandan Zeng Wenfeng Luo Can Zeng Cheng Lu Lu Lu Hongyang Huang Kaixiang Mo Julu Huang Shizhou Li Minchao Tang Tianzhun Wu Rongyun Mai Min Luo Mingzhi Xie Shan Wang Yongqiang Li Yan Lin Rong Liang 

机构地区：[1]Department of Hepatobiliary Surgery,Guangxi Medical University Cancer Hospital,Nanning 530021,China [2]Guangxi Liver Cancer Diagnosis and Treatment Project Technology Research Center,Nanning 530021,China [3]Guangxi Key Laboratory of Basic and Translational Research for Colorectal Cancer,Nanning 530021,China [4]Department of Digestive Oncology,Guangxi Medical University Cancer Hospital,Nanning 530021,China [5]Department of Research,Guangxi Medical University Cancer Hospital,Nanning 530021,China

出　　处：《Research》2025年第1期479-496,共18页研究(英文)

基　　金：granted by Guangxi Key Research and Development Plan(no.GUIKEAB19245002);National Natural Science Foundation of China(nos.82060427 and 82103297);Guangxi Natural Science Foundation(nos.2024GXNSFDA010046 and 2024GXNSFAA010401);Advanced Innovation Teams and Xinghu Scholars Program of Guangxi Medical University,Guangxi Medical University Outstanding Young Talents Training Program,Guangxi Scholarship Fund of Guangxi Education Department,Nanning Qingxiu District Science and Technology Project(nos.2020037,2020038,2021007,2021010,and 2021012);Guangxi Medical and health key discipline construction project,and Guangxi Key Laboratory of Basic and Translational Research for Colorectal Cancer.

摘　　要：Hepatocellular carcinoma(HCC)was characterized as being hypervascular.In the present study,we generated a single-cell spatial transcriptomic landscape of the vasculogenic etiology of HCC and illustrated overexpressed Golgi phosphoprotein 73(GP73)HCC cells exerting cellular communication with vascular endothelial cells with high pro-angiogenesis potential via multiple receptor-ligand interactions in the process of tumor vascular development.Specifically,we uncovered an interactive GP73-mediated regulatory network coordinated with c-Myc,lactate,Janus kinase 2/signal transducer and activator of transcription 3(JAK2/STAT3)pathway,and endoplasmic reticulum stress(ERS)signals in HCC cells and elucidated its pro-angiogenic roles in vitro and in vivo.Mechanistically,we found that GP73,the pivotal hub gene,was activated by histone lactylation and c-Myc,which stimulated the phosphorylation of downstream STAT3 by directly binding STAT3 and simultaneously enhancing glucose-regulated protein 78(GRP78)-induced ERS.STAT3 potentiates GP73-mediated pro-angiogenic functions.Clinically,serum GP73 levels were positively correlated with HCC response to anti-angiogenic regimens and were essential for a prognostic nomogram showing good predictive performance for determining 6-month and 1-year survival in patients with HCC treated with anti-angiogenic therapy.Taken together,the aforementioned data characterized the pro-angiogenic roles and mechanisms of a GP73-mediated network and proved that GP73 is a crucial tumor angiogenesis niche gene with favorable anti-angiogenic potential in the treatment of HCC.

关 键 词：hepatocellular carcinoma gp spatial transcriptomics vascular endothelial cells pro angiogenic single cell transcriptomics receptor ligand interactions 

分 类 号：R735.7[医药卫生—肿瘤]