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J Cancer 2024; 15(12):3645-3662. doi:10.7150/jca.94902 This issue Cite

Research Paper

Vesicle-mediated transport-related genes predict the prognosis and immune microenvironment in hepatocellular carcinoma

Zhiyue Ye^1#, Yang Wang^1#, Ruixin Yuan^1#, Ran Ding², Yaxin Hou¹, Luomeng Qian¹, Sihe Zhang^1✉

1. Department of Cell Biology, School of Medicine, Nankai University, Tianjin, 300071, China.
2. School of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou International Campus, Guangzhou 511442, China.
^# These authors contributed equally.

✉ Corresponding author: Prof. Si-he Zhang, Department of Cell Biology, School of Medicine, Nankai University, 94 Weijin Road, Nankai District, Tianjin, 300071, China; E-mail: sihezhangedu.cn; https://orcid.org/0000-0002-8923-1993.

Abstract

Background: Liver hepatocellular carcinoma (LIHC) is one of the leading causes of cancer-related death. The prognostic outcomes of advanced LIHC patients are poor. Hence, reliable prognostic biomarkers for LIHC are urgently needed.

Methods: Data for vesicle-mediated transport-related genes (VMTRGs) were profiled from 338 LIHC and 50 normal tissue samples downloaded from The Cancer Genome Atlas (TCGA). Univariate Cox regression and Least Absolute Shrinkage and Selection Operator (LASSO) regression analyses were performed to construct and optimize the prognostic risk model. Five GEO datasets were used to validate the risk model. The roles of the differentially expressed genes (DEGs) were investigated via Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses. Differences in immune cell infiltration between the high- and low-risk groups were evaluated using five algorithms. The “pRRophetic” was used to calculate the anticancer drug sensitivity of the two groups. Transwell and wound healing assays were performed to assess the role of GDP dissociation inhibitor 2 (GDI2) on LIHC cells.

Results: A total of 166 prognosis-associated VMTRGs were identified, and VMTRGs-based risk model was constructed for the prognosis of LIHC patients. Four VMTRGs (GDI2, DYNC1LI1, KIF2C, and RAB32) constitute the principal components of the risk model associated with the clinical outcomes of LIHC. Tumor stage and risk score were extracted as the main prognostic indicators for LIHC patients. The VMTRGs-based risk model was significantly associated with immune responses and high expression of immune checkpoint molecules. High-risk patients were less sensitive to most chemotherapeutic drugs but benefited from immunotherapies. In vitro cellular assays revealed that GDI2 significantly promoted the growth and migration of LIHC cells.

Conclusions: A VMTRGs-based risk model was constructed to predict the prognosis of LIHC patients effectively. This risk model was closely associated with the immune infiltration microenvironment. The four key VMTRGs are powerful prognostic biomarkers and therapeutic targets for LIHC.

Keywords: Vesicle-mediated transport-related genes, Prognostic signature, Immune microenvironment, Drug sensitivity, Hepatocellular carcinoma

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