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pmid:34257537

Bioinformatics Analysis of Candidate Genes and Pathways Related to Hepatocellular Carcinoma in China: A Study Based on Public Databases.

Peng Zhang · Jing Feng · Xue Wu · Weike Chu · Yilian Zhang · Ping Li

Pathology oncology research : POR · 2021 doi:10.3389/pore.2021.588532

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complete

Experiment

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Data

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Analysis

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Record details sci_version · id · kind · revision · content_hash · schema · created_at · updated_at · generator
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pmid:34257537
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2026-11-01T15:41:43Z
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2026-11-01T22:04:12Z
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title
Bioinformatics Analysis of Candidate Genes and Pathways Related to Hepatocellular Carcinoma in China: A Study Based on Public Databases.
doi
10.3389/pore.2021.588532
pmid
34257537
authors array · 6 items
[0]
Peng Zhang
[1]
Jing Feng
[2]
Xue Wu
[3]
Weike Chu
[4]
Yilian Zhang
[5]
Ping Li
journal
Pathology oncology research : POR
year
2021
abstract
Background and Objective: Hepatocellular carcinoma (HCC) is a highly aggressive malignant tumor of the digestive system worldwide. Chronic hepatitis B virus (HBV) infection and aflatoxin exposure are predominant causes of HCC in China, whereas hepatitis C virus (HCV) infection and alcohol intake are likely the main risk factors in other countries. It is an unmet need to recognize the underlying molecular mechanisms of HCC in China. Methods: In this study, microarray datasets (GSE84005, GSE84402, GSE101685, and GSE115018) derived from Gene Expression Omnibus (GEO) database were analyzed to obtain the common differentially expressed genes (DEGs) by R software. Moreover, the gene ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed by using Database for Annotation, Visualization and Integrated Discovery (DAVID). Furthermore, the protein-protein interaction (PPI) network was constructed, and hub genes were identified by the Search Tool for the Retrieval of Interacting Genes (STRING) and Cytoscape, respectively. The hub genes were verified using Gene Expression Profiling Interactive Analysis (GEPIA), UALCAN, and Kaplan-Meier Plotter online databases were performed on the TCGA HCC dataset. Moreover, the Human Protein Atlas (HPA) database was used to verify candidate genes' protein expression levels. Results: A total of 293 common DEGs were screened, including 103 up-regulated genes and 190 down-regulated genes. Moreover, GO analysis implied that common DEGs were mainly involved in the oxidation-reduction process, cytosol, and protein binding. KEGG pathway enrichment analysis presented that common DEGs were mainly enriched in metabolic pathways, complement and coagulation cascades, cell cycle, p53 signaling pathway, and tryptophan metabolism. In the PPI network, three subnetworks with high scores were detected using the Molecular Complex Detection (MCODE) plugin. The top 10 hub genes identified were CDK1, CCNB1, AURKA, CCNA2, KIF11, BUB1B, TOP2A, TPX2, HMMR and CDC45. The other public databases confirmed that high expression of the aforementioned genes related to poor overall survival among patients with HCC. Conclusion: This study primarily identified candidate genes and pathways involved in the underlying mechanisms of Chinese HCC, which is supposed to provide new targets for the diagnosis and treatment of HCC in China.
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The limma package was used to identify DEGs between normal tissues and HCC tissues in each dataset, which is based on unpaired t-test.
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sections[4] "Screening for Common Differentially Expressed Genes" paragraph 2
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The limma package was used to identify DEGs between normal tissues and HCC tissues in each dataset, which is based on unpaired t-test.
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The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material.
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sections[15] "Data Availability Statement" paragraph 2
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The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material.
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Hub Genes Identification and Prognosis Analysis
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The top 10 genes with the highest degree between HCC tissues and normal liver tissues.
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[4]
Up/down
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[0]
CDK1
[1]
cyclin-dependent kinase 1
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[3]
Cell cycle, p53 signaling pathway, Oocyte meiosis
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cyclin-B1
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kinesin family member 11
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Up
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mitotic checkpoint serine/threonine kinase B
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Cell cycle
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Up
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TOP2A
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DNA topoisomerase II alpha
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81
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Up
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TPX2
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Xenopus kinesin-like protein 2
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80
[3]
Unknown
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Up
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HMMR
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Hyaluronan mediated motility receptor
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80
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cell division cycle 45
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Cell cycle
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Survival for the ten hub genes in the Asian and White/Caucasian HCC cohorts from TCGA in Kaplan-Meier Plotter.
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Hub Genes Identification and Prognosis Analysis
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TABLE 3
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Survival for the ten hub genes in the Asian and White/Caucasian HCC cohorts from TCGA in Kaplan-Meier Plotter.
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[0]
Gene
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All (N = 364)
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Asian (N = 158)
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[0]
HR (95%CI)
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p.Value
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HR (95%CI)
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p.Value
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[0]
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2.15 (1.52–3.06)
[2]
1.1E–05
[3]
1.62 (1.01–2.59)
[4]
0.042
[5]
4.95 (2.63–9.32)
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4.7E–08
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[0]
CCNB1
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3.4E–05
[3]
1.8 (1.1–2.94)
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0.018
[5]
7.09 (3.29–15.29)
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6.3E–09
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AURKA
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1.34 (0.84–2.15)
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0.22
[5]
4.5 (2.33–8.66)
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9.6E–07
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1.91 (1.36–2.72)
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0.039
[5]
5.27 (2.53–10.98)
[6]
7.3E–07
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[0]
KIF11
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2.02 (1.42–2.85)
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5.5E–05
[3]
1.77 (1.11–2.82)
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0.014
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4.47 (2.44–8.2)
[6]
1.3E–07
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1.73 (1.01–2.96)
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0.042
[5]
4.85 (2.64–8.92)
[6]
2.4E–08
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0.00012
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2.09 (1.17–3.76)
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0.012
[5]
5.07 (2.76–9.33)
[6]
7.5E–09
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2.29 (1.62–3.24)
[2]
1.4E–06
[3]
2.54 (1.34–4.84)
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0.0032
[5]
5.95 (3.21–11.02)
[6]
1.5E–10
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[0]
HMMR
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2.29 (1.62–3.24)
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1.3E–06
[3]
2.43 (1.45–4.08)
[4]
0.00055
[5]
4.72 (2.46–9.05)
[6]
2.9E–07
[11] array · 7 items
[0]
CDC45
[1]
2.23 (1.51–3.28)
[2]
3.4E–05
[3]
1.59 (0.99–2.55)
[4]
0.053
[5]
3.94 (2.16–7.19)
[6]
1.6E–06
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Information of DEGs identified from each dataset from China.
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Identification of Common DEGs of HCC From China
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TABLE 1
caption
Information of DEGs identified from each dataset from China.
rows array · 5 items
[0] array · 6 items
[0]
GEO
[1]
Sample
[2]
City
[3]
Up-regulated genes
[4]
Down-regulated genes
[5]
Total of DEGs
[1] array · 6 items
[0]
GSE84005
[1]
HCC
[2]
Beijing
[3]
397
[4]
631
[5]
1028
[2] array · 6 items
[0]
GSE84402
[1]
HCC
[2]
Shanghai
[3]
607
[4]
1113
[5]
1720
[3] array · 6 items
[0]
GSE101685
[1]
HCC
[2]
Taipei
[3]
386
[4]
658
[5]
1044
[4] array · 6 items
[0]
GSE115018
[1]
HCC
[2]
Nanning
[3]
497
[4]
785
[5]
1282
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Hub Genes Identification and Prognosis Analysis
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The top 10 genes with the highest degree between HCC tissues and normal liver tissues.
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[0]
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[1]
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[2]
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[3]
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[4]
Up/down
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[0]
CDK1
[1]
cyclin-dependent kinase 1
[2]
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[3]
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[2] array · 5 items
[0]
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cyclin-B1
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[3]
Cell cycle, p53 signaling pathway, Oocyte meiosis
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Aurora kinase A
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[3]
Oocyte meiosis
[4]
Up
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[0]
CCNA2
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cyclin-A2
[2]
82
[3]
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[4]
Up
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[0]
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[1]
kinesin family member 11
[2]
82
[3]
Not mention
[4]
Up
[6] array · 5 items
[0]
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[1]
mitotic checkpoint serine/threonine kinase B
[2]
81
[3]
Cell cycle
[4]
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[0]
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[1]
DNA topoisomerase II alpha
[2]
81
[3]
Not mention
[4]
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[8] array · 5 items
[0]
TPX2
[1]
Xenopus kinesin-like protein 2
[2]
80
[3]
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[4]
Up
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[0]
HMMR
[1]
Hyaluronan mediated motility receptor
[2]
80
[3]
Not mention
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[0]
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79
[3]
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Hub Genes Identification and Prognosis Analysis
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TABLE 3
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Survival for the ten hub genes in the Asian and White/Caucasian HCC cohorts from TCGA in Kaplan-Meier Plotter.
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[3]
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[0]
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[2]
HR (95%CI)
[3]
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[4]
HR (95%CI)
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[2]
1.1E–05
[3]
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[4]
0.042
[5]
4.95 (2.63–9.32)
[6]
4.7E–08
[3] array · 7 items
[0]
CCNB1
[1]
2.34 (1.55–3.54)
[2]
3.4E–05
[3]
1.8 (1.1–2.94)
[4]
0.018
[5]
7.09 (3.29–15.29)
[6]
6.3E–09
[4] array · 7 items
[0]
AURKA
[1]
1.77 (1.25–2.5)
[2]
0.0011
[3]
1.34 (0.84–2.15)
[4]
0.22
[5]
4.5 (2.33–8.66)
[6]
9.6E–07
[5] array · 7 items
[0]
CCNA2
[1]
1.91 (1.36–2.72)
[2]
0.00018
[3]
1.9 (1.02–3.52)
[4]
0.039
[5]
5.27 (2.53–10.98)
[6]
7.3E–07
[6] array · 7 items
[0]
KIF11
[1]
2.02 (1.42–2.85)
[2]
5.5E–05
[3]
1.77 (1.11–2.82)
[4]
0.014
[5]
4.47 (2.44–8.2)
[6]
1.3E–07
[7] array · 7 items
[0]
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2.01 (1.42–2.86)
[2]
6.6E–05
[3]
1.73 (1.01–2.96)
[4]
0.042
[5]
4.85 (2.64–8.92)
[6]
2.4E–08
[8] array · 7 items
[0]
TOP2A
[1]
1.99 (1.39–2.86)
[2]
0.00012
[3]
2.09 (1.17–3.76)
[4]
0.012
[5]
5.07 (2.76–9.33)
[6]
7.5E–09
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[0]
TPX2
[1]
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[2]
1.4E–06
[3]
2.54 (1.34–4.84)
[4]
0.0032
[5]
5.95 (3.21–11.02)
[6]
1.5E–10
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HMMR
[1]
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[2]
1.3E–06
[3]
2.43 (1.45–4.08)
[4]
0.00055
[5]
4.72 (2.46–9.05)
[6]
2.9E–07
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CDC45
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[2]
3.4E–05
[3]
1.59 (0.99–2.55)
[4]
0.053
[5]
3.94 (2.16–7.19)
[6]
1.6E–06
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{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34257537", "kind": "science-record", "revision": 7, "content_hash": "sha256:d452bea3cd28616b7e6be7bf90aa200196bbb50943b0ee70400c53983bbde444", "created_at": "2026-11-01T15:41:43Z", "updated_at": "2026-11-01T22:04:12Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Bioinformatics Analysis of Candidate Genes and Pathways Related to Hepatocellular Carcinoma in China: A Study Based on Public Databases.", "doi": "10.3389/pore.2021.588532", "pmid": "34257537", "authors": ["Peng Zhang", "Jing Feng", "Xue Wu", "Weike Chu", "Yilian Zhang", "Ping Li"], "journal": "Pathology oncology research : POR", "year": 2021, "abstract": "Background and Objective: Hepatocellular carcinoma (HCC) is a highly aggressive malignant tumor of the digestive system worldwide. Chronic hepatitis B virus (HBV) infection and aflatoxin exposure are predominant causes of HCC in China, whereas hepatitis C virus (HCV) infection and alcohol intake are likely the main risk factors in other countries. It is an unmet need to recognize the underlying molecular mechanisms of HCC in China. Methods: In this study, microarray datasets (GSE84005, GSE84402, GSE101685, and GSE115018) derived from Gene Expression Omnibus (GEO) database were analyzed to obtain the common differentially expressed genes (DEGs) by R software. Moreover, the gene ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed by using Database for Annotation, Visualization and Integrated Discovery (DAVID). Furthermore, the protein-protein interaction (PPI) network was constructed, and hub genes were identified by the Search Tool for the Retrieval of Interacting Genes (STRING) and Cytoscape, respectively. The hub genes were verified using Gene Expression Profiling Interactive Analysis (GEPIA), UALCAN, and Kaplan-Meier Plotter online databases were performed on the TCGA HCC dataset. Moreover, the Human Protein Atlas (HPA) database was used to verify candidate genes' protein expression levels. Results: A total of 293 common DEGs were screened, including 103 up-regulated genes and 190 down-regulated genes. Moreover, GO analysis implied that common DEGs were mainly involved in the oxidation-reduction process, cytosol, and protein binding. KEGG pathway enrichment analysis presented that common DEGs were mainly enriched in metabolic pathways, complement and coagulation cascades, cell cycle, p53 signaling pathway, and tryptophan metabolism. In the PPI network, three subnetworks with high scores were detected using the Molecular Complex Detection (MCODE) plugin. The top 10 hub genes identified were CDK1, CCNB1, AURKA, CCNA2, KIF11, BUB1B, TOP2A, TPX2, HMMR and CDC45. The other public databases confirmed that high expression of the aforementioned genes related to poor overall survival among patients with HCC. 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