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肝细胞癌中溶酶体相关基因的多组学分析及实验验证

Multi-Omics Profiling and Experimental Verification of Lysosomes-Related Genes in Hepatocellular Carcinoma.

作者信息

Wang Zhiyong, Wang Guoliang, Zhao Peng, Sun Ping

机构信息

Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

出版信息

J Cell Mol Med. 2024 Dec;28(24):e70225. doi: 10.1111/jcmm.70225.

Abstract

Lysosomes play a crucial role in regulating the growth, invasion and metastasis of different tumour types. However, the specific function of lysosomes in hepatocellular carcinoma (HCC) remains uncertain. We retrieved gene expression and clinical data from the TCGA and GEO databases for HCC samples and established a new lysosome-associated prognostic therapeutic index (LAPTI) based on lysosome-related genes through machine learning. We then systematically analysed clinical characteristics, functional enrichment, tumour immune microenvironment, molecular docking, chemotherapy response and immunotherapy response in HCC. LAPTI, composed of four lysosome-related genes (CTSV, LAPTM4B, DNAJC6, AP1M2), is a reliable prognostic indicator for hepatocellular carcinoma patients and is validated in external data sets. Compared with the low LAPTI group, the high LAPTI group showed poorer prognosis and higher immune cell infiltration levels. We also observed that knocking down CTSV in vitro inhibited the proliferation and migration of hepatocellular carcinoma. This study provides valuable insights into the future clinical treatment of hepatocellular carcinoma by accurately assessing the prognosis of patients with hepatocellular carcinoma.

摘要

溶酶体在调节不同肿瘤类型的生长、侵袭和转移中起着关键作用。然而,溶酶体在肝细胞癌(HCC)中的具体功能仍不明确。我们从TCGA和GEO数据库中检索了HCC样本的基因表达和临床数据,并通过机器学习基于溶酶体相关基因建立了一个新的溶酶体相关预后治疗指数(LAPTI)。然后,我们系统地分析了HCC的临床特征、功能富集、肿瘤免疫微环境、分子对接、化疗反应和免疫治疗反应。由四个溶酶体相关基因(CTSV、LAPTM4B、DNAJC6、AP1M2)组成的LAPTI是肝细胞癌患者可靠的预后指标,并在外部数据集中得到验证。与低LAPTI组相比,高LAPTI组显示出更差的预后和更高的免疫细胞浸润水平。我们还观察到,体外敲低CTSV可抑制肝细胞癌的增殖和迁移。本研究通过准确评估肝细胞癌患者的预后,为肝细胞癌未来的临床治疗提供了有价值的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e4d/11655306/18b63e15f302/JCMM-28-e70225-g004.jpg

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