NPC1 promotes autophagy with tumor promotion and acts as a prognostic model for hepatocellular carcinoma.

Autor: Xu J; Department of Hepatobiliary Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, China., Chen F; Department of Nuclear Medicine, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, China., Zhu W; Department of Gastrointestinal Surgery, Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China., Zhang W; Department of Nuclear Medicine, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, China. Electronic address: 875099223@qq.com.
Jazyk: angličtina
Zdroj: Gene [Gene] 2024 Mar 01; Vol. 897, pp. 148050. Date of Electronic Publication: 2023 Nov 30.
DOI: 10.1016/j.gene.2023.148050
Abstrakt: Background: more and more studies have indicated that autophagy plays a crucial role in hepatocellular carcinoma (HCC) in recent years. Hence, our study aimed to establish a prognostic signature for HCC based on autophagy-related genes (ARGs) in order to predict the prognosis of HCC.
Methods: All original gene-expression data and clinical information were downloaded from The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC) and Gene Expression Omnibus (GEO). ARGs were obtained from the Human Autophagy Database (HADb). Univariate Cox regression analysis, Least absolute shrinkage and selection operator (LASSO) and Principal Component Analysis (PCA) analysis were performed to identify and validate the validity and reliability of our eight-gene signature, Gene Set Enrichment Analysis (GSEA) was used to perform enrichment analysis by comparing high-risk and low-risk groups in KEGG (Kyoto Encyclopedia of Genes and Genomes) and GO (Gene Ontology) gene sets. Finally, we verified the gene (NPC1) by functional experiments in vitro and in vivo.
Results: 8 ARGs were identified for establishing an eight-gene signature. Then, we validated our eight-gene signature in training, internal, external, and entire testing cohorts. Besides, we also explored the relationships between the eight-gene signature and immune infiltration or immune checkpoints. We also identified NPC1 was closely related to Activated CD4 T cell and Type I IFN Response, and higher expressed level of HCC patients was more sensitive to CTLA4 and TNFRSF9 immune checkpoint inhibitors. NPC1 is highly expressed in HCC cells and tumor tissues, which promotes the proliferation, migration, and invasion of tumor cells by activating autophagy..
Conclusion: 8 ARGs were used to establish a gene signature to predict the prognosis of HCC. we inferred that NPC1 can promote late autophagy, it could be a future novel therapeutic target of HCC.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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