Abstract
Emerging evidence indicates that various functional genes with altered expression are involved in the tumor progression of human cancers. This study is aimed at identifying novel key genes that may be used for hepatocellular carcinoma (HCC) diagnosis, prognosis, and targeted therapy. This study included 3 expression profiles (GSE45267, GSE74656, and GSE84402), which were obtained from the Gene Expression Omnibus (GEO). GEO2R was used to analyze the differentially expressed genes (DEGs) between HCC and normal samples. The functional and pathway enrichment analysis was performed by the Database for Annotation, Visualization and Integrated Discovery. A protein-protein interaction (PPI) network of the identified DEGs was constructed using the Search Tool for the Retrieval of Interacting Gene, and hub genes were identified. ONCOMINE and CCLE databases were used to verify the expression of the hub genes in HCC tissues and cells. Kaplan-Meier plotter was used to assess the effects of the hub genes on the overall survival of HCC patients. A total of 99 DEGs were identified from the 3 expression profiles. These DEGs were enriched with functional processes and pathways related to HCC pathogenesis. From the PPI network, 5 hub genes were identified. The expression of the 5 hub genes was all upregulated in HCC tissues and cells compared with the control tissues and cells. Kaplan-Meier survival curves indicated that high expression of cyclin-dependent kinase (CDK1), cyclin B1 (CCNB1), cyclin B2 (CCNB2), MAD2 mitotic arrest deficient-like 1 (MAD2L1), and topoisomerase IIα (TOP2A) predicted poor overall survival in HCC patients (all log-rank P < 0.01). These results revealed that the DEGs may serve as candidate key genes during HCC pathogenesis. The 5 hub genes, including CDK1, CCNB1, CCNB2, MAD2L1, and TOP2A, may serve as promising prognostic biomarkers in HCC.
Highlights
Hepatocellular carcinoma (HCC) remains a serious health burden and is the second leading cause of cancer mortality worldwide [1]
To confirm the clinical significance of the 5 hub genes in the prognosis of HCC, data from The Cancer Genome Atlas (TCGA) database were further assessed using the Gene Expression Profiling Interactive Analysis (GEPIA), which is a webbased tool to deliver fast and customizable functionalities based on TCGA data [27]
Ba and colleagues have reported that the serum expression of Golgi protein-73 (GP73) was higher in HCC patients compared with healthy individuals and serves as a novel biomarker for HCC diagnosis [30]
Summary
Hepatocellular carcinoma (HCC) remains a serious health burden and is the second leading cause of cancer mortality worldwide [1]. It is generally considered that tumorigenesis is a complex process with a wide spectrum of genetic alterations [5]. These genes typically exhibit aberrant expression patterns and have clinical significance in cancer diagnosis and prognosis [6]. The high expression of peroxiredoxin 1 (Prdx1) is associated with tumor development and overall survival of HCC patients and serves as a candidate biomarker for the screening and prediction of this malignancy [7]. Upregulated expression of distal-less homeobox gene 4 (DLX4) in HCC samples has been shown to be associated with poor prognosis of HCC patients [9].
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