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ISSN (Print): 1573-4099
ISSN (Online): 1875-6697

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Research Article

Construction of a Combined Hypoxia-related Genes Model for Hepatocellular Carcinoma Prognosis

Author(s): Liping Ren, Xianrun Pan, Lin Ning, Di Gong, Jian Huang, Kejun Deng*, Lei Xie* and Yang Zhang*

Volume 19, Issue 2, 2023

Published on: 30 December, 2022

Page: [150 - 161] Pages: 12

DOI: 10.2174/1573409919666221223123610

Price: $65

Abstract

Background: Hepatocellular carcinoma (HCC) is the most common liver malignancy where tumorigenesis and metastasis are believed to be tied to the hallmarks of hypoxia and tumor microenvironment (TME).

Methods: In this study, to investigate the relationships among hypoxia, TME, and HCC prognosis, we collected two independent datasets from a public database (TCGA-LIHC for identification, GSE14520 for validation) and identified the hypoxia-related differentially expressed genes (DEGs) from the TCGA data, and the univariable Cox regression and lasso regression analyses were performed to construct the prognosis model. An HCC prognosis model with 4 hypoxiarelated DEGs ("NDRG1", "ENO1", "SERPINE1", "ANXA2") was constructed, and high- and low-risk groups of HCC were established by the median of the model risk score.

Results: The survival analysis revealed significant differences between the two groups in both datasets, with the results of the AUC of the ROC curve of 1, 3, and 5 years in two datasets indicating the robustness of the prognosis model. Meanwhile, for the TCGA-LIHC data, the immune characteristics between the two groups revealed that the low-risk group presented higher levels of activated NK cells, monocytes, and M2 macrophages, and 7 immune checkpoint genes were found upregulated in the high-risk group. Additionally, the two groups have no difference in molecular characteristics (tumor mutational burden, TMB). The proportion of recurrence was higher in the high-risk group, and the correlation between the recurrence month and risk score was negative, indicating high-risk correlates with a short recurrence month.

Conclusion: In summary, this study shows the association among hypoxic signals, TME, and HCC prognosis and may help reveal potential regulatory mechanisms between hypoxia, tumorigenesis, and metastasis in HCC. The hypoxia-related model demonstrated the potential to be a predictor and drug target of prognosis.

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