Screening and Identification of Potential Biomarkers in Hepatitis B Virus-Related Hepatocellular Carcinoma by Bioinformatics Analysis

Abstract

Hepatocellular carcinoma (HCC) is one of the most lethal cancers globally. Hepatitis B virus (HBV) infection might cause chronic hepatitis and cirrhosis, leading to HCC. To screen prognostic genes and therapeutic targets for HCC by bioinformatics analysis and determine the mechanisms underlying HBV-related HCC, three high-throughput RNA-seq based raw datasets, namely GSE25599, GSE77509, and GSE94660, were obtained from the Gene Expression Omnibus database, and one RNA-seq raw dataset was acquired from The Cancer Genome Atlas (TCGA). Overall, 103 genes were upregulated and 127 were down-regulated. A protein-protein interaction (PPI) network was established using Cytoscape software, and 12 pivotal genes were selected as hub genes. The 230 differentially expressed genes and 12 hub genes were subjected to functional and pathway enrichment analyses, and the results suggested that cell cycle, nuclear division, mitotic nuclear division, oocyte meiosis, retinol metabolism, and p53 signaling-related pathways play important roles in HBV-related HCC progression. Further, among the 12 hub genes, kinesin family member 11 (KIF11), TPX2 microtubule nucleation factor (TPX2), kinesin family member 20A (KIF20A), and cyclin B2 (CCNB2) were identified as independent prognostic genes by survival analysis and univariate and multivariate Cox regression analysis. These four genes showed higher expression levels in HCC than in normal tissue samples, as identified upon analyses with Oncomine. In addition, in comparison with normal tissues, the expression levels of KIF11, TPX2, KIF20A, and CCNB2 were higher in HBV-related HCC than in HCV-related HCC tissues. In conclusion, our results suggest that KIF11, TPX2, KIF20A, and CCNB2 might be involved in the carcinogenesis and development of HBV-related HCC. They can thus be used as independent prognostic genes and novel biomarkers for the diagnosis of HBV-related HCC and development of pertinent therapeutic strategies.

Bioinformatics Prediction and Experimental Verification Identify MAD2L1 and CCNB2 as Diagnostic Biomarkers of Rhabdomyosarcoma

“…Abnormal expression of MAD2 may be related to the pleomorphic features and atypical mitosis of soft tissue sarcomas and the progression of translocation-associated highgrade tumours [14]. The cell cycle-related molecule CCNB2 is a potential diagnostic or prognostic marker for various cancers, including liver cancer [15], melanoma [16] and lung cancer [17]. However, the clinical roles of MAD2L1 and CCNB2 in RMS are unclear.…”

Comprehensive analysis of a TPX2-related TRHDE-AS1/PKIA ceRNA network involving prognostic signatures in Hepatitis B virus-infected hepatocellular carcinoma

“…Previous literature identified TPX2 as a DEG in HBV-infected HCC specimens ( Zeng et al., 2020 ). The raw data (GSE25599 and GSE94660) downloaded from SRA (SRP004768 and SRP099053) was subjected to analysis with limma R package.…”

“…TPX2 recruits Aurora-A kinase to microtubules and drives the activation of Aurora-A kinase during mitosis ( Asteriti et al., 2010 ). Accumulating analysis has shown that high expression of TPX2 is involved in worse prognosis of patients with HBV-related HCC ( Zeng et al., 2020 ). In this research, we utilized the GEO RNA-seq data and the Cancer Genome Atlas (TCGA) HCC cohort to confirm the difference of TPX2 expression levels between HBV-related HCC tissues and normal samples, and screen differential expressed lncRNAs (DElncRNAs), DEmicroRNAs and DEmRNAs in TPX2 high vs TPX2 low expression groups ( Figure 1 ).…”

A GSVA based gene set synergizing with CD4+T cell bearing harmful factors yield risk signals in HBV related diseases via amalgamation of artificial intelligence

“…15 hub genes with highest Maximal Clique Centrality (MCC) score including chemokines-related gene cluster (CXCL6, CXCL9, CXCL10, CXCL11, CXCR4, CCL19, CCL20) and ECM-related gene cluster (COL1A1, COL1A2, SPP1, VCAN, LUM, SOX9, THBS1, THBS2) were screened out of 64 DEGs using Cytohubba plugin according to the previous studies (Fig. 2A, B) (47,48) . The association of 15 hub genes in patients with differential grading scores (G0-G4 phases, GSE84044) were also investigated and almost all of these genes were significantly up-regulated in G2, G3 and G4 group when compared with G0 group, respectively (Fig.…”