Abstract
Objective To evaluate the association between upregulated differentially expressed genes (DEGs) and the outcomes of patients with hepatocellular carcinoma (HCC). Methods Using Gene Expression Omnibus (GEO) datasets including GSE45436, GSE55092, GSE60502, GSE84402, and GSE17548, we detected upregulated DEGs in tumors. KEGG, GO, and Reactome enrichment analysis of the DEGs was conducted to clarify their function. The impact of the upregulated DEGs on patients' survival was analyzed based on TCGA profile. Results 161 shared upregulated DEGs were identified among GSE45436, GSE55092, GSE60502, and GSE84402 profiles. Cell cycle was the shared pathway/biological process in the gene sets investigation among databases of KEGG, GO, and Reactome. After being validated in GSE17548, 13 genes including BUB1B, CCNA2, CCNB1, CCNE2, CDC20, CDC6, CDC7, CDK1, CDK4, CDKN2A, CHEK1, MAD2L1, and MCM3 in cell cycle pathway were shared in the three databases for enrichment. The expression of BUB1B, CCNB1, CDC7, CDC20, and MCM3 was upregulated in HCC tissues when compared with adjacent normal tissues in 6.67%, 7.5%, 8.06%, 5.56%, and 9.72% of HCC patients, respectively. Overexpression of BUB1B, CCNB1, CDC7, CDC20, and MCM3 in HCC tissues accounted for poorer overall survival (OS) and disease-free survival (DFS) in HCC patients (all log rank P < 0.05). BUB1B, CCNB1, CDC7, CDC20, and MCM3 were all overexpressed in HCC patients with neoplasm histologic grade G3-4 compared to those with G1-2 (all P < 0.05). BUB1B, CCNB1, and CDC20 were significantly upregulated in HCC patients with vascular invasion (all P < 0.05). Additionally, levels of BUB1B, CCNB1, CDC7, and CDC20 were significantly higher in HCC patients deceased, recurred, or progressed (all P < 0.05). Conclusion Correlated with advanced histologic grade and/or vascular invasion, upregulation of BUB1B, CCNB1, CDC7, CDC20, and MCM3 in HCC tissues predicted worse OS and DFS in HCC patients. These genes could be novel therapeutic targets for HCC treatment.
Highlights
Hepatocellular carcinoma (HCC) is the fifth most common cancer and the second most common cause of cancer-related deaths [1,2,3]
To investigate differentially expressed genes (DEGs) in transcriptome between tumor tissues and adjacent normal tissues in HCC patients, Affy, AffyPLM, and Limma packages were used for quality assessment and identifying DEGs of tumor and adjacent normal samples in each Gene Expression Omnibus (GEO) profile based on the microarray platform
Overexpression of 1779, 770, 1306, and 844 genes was identified in GSE45436, GSE55092, GSE60502, and GSE84402 profiles, respectively. 161 shared genes were identified among these four GEO profiles using Venn diagram performance (Figure 1(a) and Supplementary Table 1)
Summary
Hepatocellular carcinoma (HCC) is the fifth most common cancer and the second most common cause of cancer-related deaths [1,2,3]. In the past two decades, a marked increase in HCC-related annual death rates was observed [2,3,4]. Big data bioinformatics of molecular targets and networks have increasingly gained attention [6, 7], due to the introduction of large scale molecular analysis platforms [8]; human genomes resources of cancers including HCC are publicly available. This tremendous amount of molecular data provides a rich source to better understand the molecular basis of HCC and to identify novel genomic targets for therapeutic intervention.
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