A hypoxia-related signature for clinically predicting diagnosis, prognosis and immune microenvironment of hepatocellular
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Journal of Translational Medicine Open Access
RESEARCH
A hypoxia‑related signature for clinically predicting diagnosis, prognosis and immune microenvironment of hepatocellular carcinoma patients Baohui Zhang1†, Bufu Tang2†, Jianyao Gao3, Jiatong Li4, Lingming Kong5 and Ling Qin1*
Abstract Background: Hypoxia plays an indispensable role in the development of hepatocellular carcinoma (HCC). However, there are few studies on the application of hypoxia molecules in the prognosis predicting of HCC. We aim to identify the hypoxia-related genes in HCC and construct reliable models for diagnosis, prognosis and recurrence of HCC patients as well as exploring the potential mechanism. Methods: Differentially expressed genes (DEGs) analysis was performed using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database and four clusters were determined by a consistent clustering analysis. Three DEGs closely related to overall survival (OS) were identified using Cox regression and LASSO analysis. Then the hypoxia-related signature was developed and validated in TCGA and International Cancer Genome Consortium (ICGC) database. The Gene Set Enrichment Analysis (GSEA) was performed to explore signaling pathways regulated by the signature. CIBERSORT was used for estimating the fractions of immune cell types. Results: A total of 397 hypoxia-related DEGs in HCC were detected and three genes (PDSS1, CDCA8 and SLC7A11) among them were selected to construct a prognosis, recurrence and diagnosis model. Then patients were divided into high- and low-risk groups. Our hypoxia-related signature was significantly associated with worse prognosis and higher recurrence rate. The diagnostic model also accurately distinguished HCC from normal samples and nodules. Furthermore, the hypoxia-related signature could positively regulate immune response. Meanwhile, the high-risk group had higher fractions of macrophages, B memory cells and follicle-helper T cells, and exhibited higher expression of immunocheckpoints such as PD1and PDL1. Conclusions: Altogether, our study showed that hypoxia-related signature is a potential biomarker for diagnosis, prognosis and recurrence of HCC, and it provided an immunological perspective for developing personalized therapies. Keyword: Hypoxia, Hepatocellular carcinoma, Prognostic, Diagnostic, Immune microenvironment
*Correspondence: [email protected] † Baohui Zhang and Bufu Tang contributed equally to this work 1 Department of Physiology, School of Life Science, China Medical University, No. 77 Puhe Road, Shenyang North New AreaLiaoning Province, Shenyang 110122, People’s Republic of China Full list of author information is available at the end of the article
Background Hepatocellular carcinoma (HCC) accounts for 85% of liver cancers, and the disease burden of HCC is increasing globally [1]. Although progress on treatment strategies for HCC has been made, the overall 5-year survival rate for HCC patients remains less than
© The Author(s) 2020. This article is licensed under a Creative Common
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