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pmid:30369945

Identification of Candidate Biomarkers Correlated With the Pathogenesis and Prognosis of Non-small Cell Lung Cancer via Integrated Bioinformatics Analysis.

Mengwei Ni · Xinkui Liu · Jiarui Wu · Dan Zhang · Jinhui Tian · Ting Wang · Shuyu Liu · Ziqi Meng · Kaihuan Wang · Xiaojiao Duan · Wei Zhou · Xiaomeng Zhang

Frontiers in genetics · 2018 doi:10.3389/fgene.2018.00469

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Experiment

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Data

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title
Identification of Candidate Biomarkers Correlated With the Pathogenesis and Prognosis of Non-small Cell Lung Cancer via Integrated Bioinformatics Analysis.
doi
10.3389/fgene.2018.00469
pmid
30369945
authors array · 12 items
[0]
Mengwei Ni
[1]
Xinkui Liu
[2]
Jiarui Wu
[3]
Dan Zhang
[4]
Jinhui Tian
[5]
Ting Wang
[6]
Shuyu Liu
[7]
Ziqi Meng
[8]
Kaihuan Wang
[9]
Xiaojiao Duan
[10]
Wei Zhou
[11]
Xiaomeng Zhang
journal
Frontiers in genetics
year
2018
abstract
Background and Objective: Non-small cell lung cancer (NSCLC) accounts for 80-85% of all patients with lung cancer and 5-year relative overall survival (OS) rate is less than 20%, so that identifying novel diagnostic and prognostic biomarkers is urgently demanded. The present study attempted to identify potential key genes associated with the pathogenesis and prognosis of NSCLC. Methods: Four GEO datasets (GSE18842, GSE19804, GSE43458, and GSE62113) were obtained from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) between NSCLC samples and normal ones were analyzed using limma package, and RobustRankAggreg (RRA) package was used to conduct gene integration. Moreover, Search Tool for the Retrieval of Interacting Genes database (STRING), Cytoscape, and Molecular Complex Detection (MCODE) were utilized to establish protein-protein interaction (PPI) network of these DEGs. Furthermore, functional enrichment and pathway enrichment analyses for DEGs were performed by Funrich and OmicShare. While the expressions and prognostic values of top genes were carried out through Gene Expression Profiling Interactive Analysis (GEPIA) and Kaplan Meier-plotter (KM) online dataset. Results: A total of 249 DEGs (113 upregulated and 136 downregulated) were identified after gene integration. Moreover, the PPI network was established with 166 nodes and 1784 protein pairs. Topoisomerase II alpha (TOP2A), a top gene and hub node with higher node degrees in module 1, was significantly enriched in mitotic cell cycle pathway. In addition, Interleukin-6 (IL-6) was enriched in amb2 integrin signaling pathway. The mitotic cell cycle was the most significant pathway in module 1 with the highest P-value. Besides, five hub genes with high degree of connectivity were selected, including TOP2A, CCNB1, CCNA2, UBE2C, and KIF20A, and they were all correlated with worse OS in NSCLC. Conclusion: The results showed that TOP2A, CCNB1, CCNA2, UBE2C, KIF20A, and IL-6 may be potential key genes, while the mitotic cell cycle pathway may be a potential pathway contribute to progression in NSCLC. Further, it could be used as a new biomarker for diagnosis and to direct the synthesis medicine of NSCLC.
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Limma package (Ritchie et al., 2015) in R/Bioconductor software was applied to perform the normalization and log2 conversion for the matrix data of each GEO dataset, and the DEGs in every microarray were also screened by the limma package.
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sections[4] "Integrated Analysis of Microarray Datasets" paragraph 2
quote
Limma package (Ritchie et al., 2015) in R/Bioconductor software was applied to perform the normalization and log2 conversion for the matrix data of each GEO dataset, and the DEGs in every microarray were also screened by the limma package.
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sections[3] "Gene Expression Profile Data" paragraph 2
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The gene expression profile data (GSE18842, GSE19804, GSE43458, and GSE62113) were obtained from Gene Expression Omnibus (GEO1) (Schminke et al., 2015).
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Gene Expression Profile Data
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Gene Expression Profile Data
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The gene expression profile data characteristics.
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Hub genes with high degree of connectivity.
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PPI Network Analysis and Module Analysis
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Table 2
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Hub genes with high degree of connectivity.
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{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:30369945", "kind": "science-record", "revision": 9, "content_hash": "sha256:3981c72db981475635638f511a08897a5721f3be3ded23c8cefc8abe0b1af979", "created_at": "2026-11-01T15:40:38Z", "updated_at": "2026-11-01T22:43:36Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of Candidate Biomarkers Correlated With the Pathogenesis and Prognosis of Non-small Cell Lung Cancer via Integrated Bioinformatics Analysis.", "doi": "10.3389/fgene.2018.00469", "pmid": "30369945", "authors": ["Mengwei Ni", "Xinkui Liu", "Jiarui Wu", "Dan Zhang", "Jinhui Tian", "Ting Wang", "Shuyu Liu", "Ziqi Meng", "Kaihuan Wang", "Xiaojiao Duan", "Wei Zhou", "Xiaomeng Zhang"], "journal": "Frontiers in genetics", "year": 2018, "abstract": "Background and Objective: Non-small cell lung cancer (NSCLC) accounts for 80-85% of all patients with lung cancer and 5-year relative overall survival (OS) rate is less than 20%, so that identifying novel diagnostic and prognostic biomarkers is urgently demanded. The present study attempted to identify potential key genes associated with the pathogenesis and prognosis of NSCLC. Methods: Four GEO datasets (GSE18842, GSE19804, GSE43458, and GSE62113) were obtained from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) between NSCLC samples and normal ones were analyzed using limma package, and RobustRankAggreg (RRA) package was used to conduct gene integration. Moreover, Search Tool for the Retrieval of Interacting Genes database (STRING), Cytoscape, and Molecular Complex Detection (MCODE) were utilized to establish protein-protein interaction (PPI) network of these DEGs. Furthermore, functional enrichment and pathway enrichment analyses for DEGs were performed by Funrich and OmicShare. While the expressions and prognostic values of top genes were carried out through Gene Expression Profiling Interactive Analysis (GEPIA) and Kaplan Meier-plotter (KM) online dataset. Results: A total of 249 DEGs (113 upregulated and 136 downregulated) were identified after gene integration. Moreover, the PPI network was established with 166 nodes and 1784 protein pairs. Topoisomerase II alpha (TOP2A), a top gene and hub node with higher node degrees in module 1, was significantly enriched in mitotic cell cycle pathway. In addition, Interleukin-6 (IL-6) was enriched in amb2 integrin signaling pathway. The mitotic cell cycle was the most significant pathway in module 1 with the highest P-value. Besides, five hub genes with high degree of connectivity were selected, including TOP2A, CCNB1, CCNA2, UBE2C, and KIF20A, and they were all correlated with worse OS in NSCLC. Conclusion: The results showed that TOP2A, CCNB1, CCNA2, UBE2C, KIF20A, and IL-6 may be potential key genes, while the mitotic cell cycle pathway may be a potential pathway contribute to progression in NSCLC. Further, it could be used as a new biomarker for diagnosis and to direct the synthesis medicine of NSCLC.", "claims": [{"id": "claim-method", "statement": "Limma package (Ritchie et al., 2015) in R/Bioconductor software was applied to perform the normalization and log2 conversion for the matrix data of each GEO dataset, and the DEGs in every microarray were also screened by the limma package.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:30369945", "locator": "sections[4] \"Integrated Analysis of Microarray Datasets\" paragraph 2", "quote": "Limma package (Ritchie et al., 2015) in R/Bioconductor software was applied to perform the normalization and log2 conversion for the matrix data of each GEO dataset, and the DEGs in every microarray were also screened by the limma package."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The gene expression profile data (GSE18842, GSE19804, GSE43458, and GSE62113) were obtained from Gene Expression Omnibus (GEO1) (Schminke et al., 2015).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:30369945", "locator": "sections[3] \"Gene Expression Profile Data\" paragraph 2", "quote": "The gene expression profile data (GSE18842, GSE19804, GSE43458, and GSE62113) were obtained from Gene Expression Omnibus (GEO1) (Schminke et al., 2015)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": null, "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:30369945"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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