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pmid:35571642
Identification of genes and pathways leading to poor prognosis of non-small cell lung cancer using integrated bioinformatics analysis.
Shengjin Cui · Shuang Lou · Jingying Feng · Xi Tang · Xiaowei Xiao · Rong Huang · Weiquan Guo · Yiwen Zhou · Feixia Huang
Translational cancer research · 2022 doi:10.21037/tcr-21-1986
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Experiment
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Complete file
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Herein, our study aimed to identify significant genes with poor outcome and underlying mechanisms in NSCLC using bioinformatics analyses.\nMethods: Gene expression profiles (GSE33532, GSE19188, GSE102287, GSE27262), including 319 NSCLC and 232 adjacent lung tissues, were downloaded from the GEO database. Differentially expressed genes (DEGs) were identified by the GEO2R online tool. Functional and pathway enrichment analyses were performed via the DAVID database. The protein-protein interactions (PPIs) of these DEGs were constructed by the STRING website and visualized by the Cytoscape software platform. The expression of hub genes in NSCLC was validated through the GEPIA database. Kaplan-Meier plotter was used to analyse the survival rate with multivariate Cox regression. The expression of protein tyrosine kinase 2 (PTK2) in NSCLC and adjacent lung tissues was evaluated on the UALCAN database platform.\nResults: A total of 225 significant DEGs were obtained between NSCLC and adjacent lung tissues, containing 52 upregulated genes and 173 downregulated genes. The DEGs were clustered based on functions and signaling pathways that may be closely associated with NSCLC occurrence. A total of 174 DEGs were identified from the PPI network complex. Top 10 hub genes were selected by CytoHubba plugin. As independent predictors, seven genes (COL1A1, ADAM12, VWF, OGN, EDN1, CAV1, ITGA8) were associated with poor prognosis in NSCLC via multivariate Cox regression (P<0.01). Four genes (VWF, CAV1, ITGA8, COL1A1) were found to be significantly enriched in the focal adhesion pathway (P=1.04E-04) and to be upstream regulators of PTK2. PTK2 was upregulated in NSCLC and associated with poor survival prognosis in lung squamous cell carcinoma (LUSC).\nConclusions: Taken together, the important genes and pathways in NSCLC were identified by using integrated bioinformatics analysis. PTK2 could be a key gene associated with the biological process of NSCLC formation and progression and a potential therapeutic target for NSCLC treatment.", "claims": [{"id": "claim-method", "statement": "DEGs between NSCLC and adjacent lung tissue were filtered via the GEO2R online tool.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35571642", "locator": "sections[2] \"Methods\" paragraph 2", "quote": "DEGs between NSCLC and adjacent lung tissue were filtered via the GEO2R online tool."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Data Sharing Statement: Available at https://tcr.amegroups.com/article/view/10.21037/tcr-21-1986/dss", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35571642", "locator": "sections[19] \"fn-group\" paragraph 1", "quote": "Data Sharing Statement: Available at https://tcr.amegroups.com/article/view/10.21037/tcr-21-1986/dss"}], "state": "complete"}, {"id": "claim-target-result", "statement": "A total of 225 common DEGs were identified through the Venn diagram database, including 52 upregulated genes and 173 downregulated genes in NSCLC tissue compared to adjacent lung tissues (Table 1, Figure 1).", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:35571642", "locator": "sections[10] \"Microarray data information and DEGs identification\" paragraph 2", "quote": "A total of 225 common DEGs were identified through the Venn diagram database, including 52 upregulated genes and 173 downregulated genes in NSCLC tissue compared to adjacent lung tissues (Table 1, Figure 1)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "A total of 225 common DEGs were identified through the Venn diagram database, including 52 upregulated genes and 173 downregulated genes in NSCLC tissue compared to adjacent lung tissues (Table 1, Figure 1).", "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:35571642"], "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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