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pmid:37583423

Bioinformatics-based screening of key genes for transformation of tyrosine kinase inhibitor-resistant lung adenocarcinoma to small cell lung cancer.

Ying Zhang · Qiang Chen · Ting Huang · Di Zhu · Yuanzhi Lu

Frontiers in medicine · 2023 doi:10.3389/fmed.2023.1203461

Paper

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Experiment

complete

Data

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title
Bioinformatics-based screening of key genes for transformation of tyrosine kinase inhibitor-resistant lung adenocarcinoma to small cell lung cancer.
doi
10.3389/fmed.2023.1203461
pmid
37583423
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Ying Zhang
[1]
Qiang Chen
[2]
Ting Huang
[3]
Di Zhu
[4]
Yuanzhi Lu
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Frontiers in medicine
year
2023
abstract
Purpose: Lung adenocarcinoma (LUAD) is a common type of lung cancer. Cancer in a small number of patients with EGFR mutations will transform from LUAD to small cell lung cancer (SCLC) during epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) therapiesr. The purpose of the present study was to identify the core genes related to the transformation of LUAD into SCLC and to explore the associated molecular mechanisms. Methods: GSE29016, GSE1037, GSE6044 and GSE40275 mRNA microarray datasets from Gene Expression Omnibus (GEO) were analyzed to obtain differentially expressed genes (DEGs) between LUAD and SCLC tissues, and the results were used for network analysis of protein-protein interactions (PPIs). After identifying the hub gene by STRING and Cytoscape platform, we explored the relationship between hub genes and the occurrence and development of SCLC. Finally, the obtained hub genes were validated in treated LUAD cells. Results: A total of 41 DEGs were obtained, four hub genes (EZH2, NUSAP1, TTK and UBE2C) were identified, and related prognostic information was obtained. The coexpressed genes of the hub gene set were further screened, and the analysis identified many genes related to the cell cycle. Subsequently, LUAD cell models with TP53 and RB1 inactivation and overexpression of ASCL1 were constructed, and then the expression of hub genes was detected, the results showed that the four hub genes were all elevated in the established cell model. Conclusion: EZH2, NUSAP1, TTK and UBE2C may affect the transformation of LUAD to SCLC and represent new candidate molecular markers for the occurrence and development of SCLC.
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Student’s two-tailed t test was selected for statistical analysis, and p < 0.05 was considered statistically significant.
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The original contributions presented in the study are included in the article/Supplementary material. The RNA sequencing data provided in the research are stored in the GEO repository, and the GEO accession number is GSE232387; The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE (56) partner repository with the dataset identifier PXD042073. Further inquiries can be directed to the corresponding author.
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The original contributions presented in the study are included in the article/Supplementary material. The RNA sequencing data provided in the research are stored in the GEO repository, and the GEO accession number is GSE232387; The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE (56) partner repository with the dataset identifier PXD042073. Further inquiries can be directed to the corresponding author.
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title
Mechanism of TP53 and RB1 inactivation-induced neuroendocrine phenotype transformation in TKI-resistant lung adenocarcinoma
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2026-11-01T19:09:50Z
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identifier_resolution_only_no_download_no_licence_read
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Student’s two-tailed t test was selected for statistical analysis, and p < 0.05 was considered statistically significant.
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The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: deseq2.
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The original contributions presented in the study are included in the article/Supplementary material. The RNA sequencing data provided in the research are stored in the GEO repository, and the GEO accession number is GSE232387; The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE (56) partner repository with the dataset identifier PXD042073. Further inquiries can be directed to the corresponding author.
basis
The paper names GSE29016, GSE1037, GSE6044, GSE40275, GSE232387, PXD042073 in Gene Expression Omnibus (GEO) and the accession resolves in the repository. No dataset was downloaded and no licence was read.
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minimax
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minimax
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in (Gibco, Grand Island, NY, United States). Cell lines were cultured in a 37°C incubator with 5% CO2. Sequencing
[1]
Island, NY, United States). Cell lines were cultured in a 37°C incubator with 5% CO2. Sequencing ana
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ells infected with lentivirus expressing RB1-shRNA (n = 3) or pLKO.1-shRNA (n = 3) were culture
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virus expressing RB1-shRNA (n = 3) or pLKO.1-shRNA (n = 3) were cultured, and total RNA was ext
[2]
ells infected with lentivirus expressing RB1-shRNA (n = 3) and pLKO.1-shRNA (n = 3) were analyz
[3]
irus expressing RB1-shRNA (n = 3) and pLKO.1-shRNA (n = 3) were analyzed using an Illumina HiSe
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:37583423", "kind": "science-record", "revision": 4, "content_hash": "sha256:0e4ba129a3d687375af7a1b0ff6f4c32b6da741a81cec8a35659cc99f834c00a", "created_at": "2026-11-01T19:02:22Z", "updated_at": "2026-11-01T22:10:05Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Bioinformatics-based screening of key genes for transformation of tyrosine kinase inhibitor-resistant lung adenocarcinoma to small cell lung cancer.", "doi": "10.3389/fmed.2023.1203461", "pmid": "37583423", "authors": ["Ying Zhang", "Qiang Chen", "Ting Huang", "Di Zhu", "Yuanzhi Lu"], "journal": "Frontiers in medicine", "year": 2023, "abstract": "Purpose: Lung adenocarcinoma (LUAD) is a common type of lung cancer. Cancer in a small number of patients with EGFR mutations will transform from LUAD to small cell lung cancer (SCLC) during epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) therapiesr. The purpose of the present study was to identify the core genes related to the transformation of LUAD into SCLC and to explore the associated molecular mechanisms.\nMethods: GSE29016, GSE1037, GSE6044 and GSE40275 mRNA microarray datasets from Gene Expression Omnibus (GEO) were analyzed to obtain differentially expressed genes (DEGs) between LUAD and SCLC tissues, and the results were used for network analysis of protein-protein interactions (PPIs). After identifying the hub gene by STRING and Cytoscape platform, we explored the relationship between hub genes and the occurrence and development of SCLC. Finally, the obtained hub genes were validated in treated LUAD cells.\nResults: A total of 41 DEGs were obtained, four hub genes (EZH2, NUSAP1, TTK and UBE2C) were identified, and related prognostic information was obtained. The coexpressed genes of the hub gene set were further screened, and the analysis identified many genes related to the cell cycle. Subsequently, LUAD cell models with TP53 and RB1 inactivation and overexpression of ASCL1 were constructed, and then the expression of hub genes was detected, the results showed that the four hub genes were all elevated in the established cell model.\nConclusion: EZH2, NUSAP1, TTK and UBE2C may affect the transformation of LUAD to SCLC and represent new candidate molecular markers for the occurrence and development of SCLC.", "claims": [{"id": "claim-method", "statement": "Student’s two-tailed t test was selected for statistical analysis, and p < 0.05 was considered statistically significant.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37583423", "locator": "sections[17] \"Statistical analysis\" paragraph 2", "quote": "Student’s two-tailed t test was selected for statistical analysis, and p < 0.05 was considered statistically significant."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The original contributions presented in the study are included in the article/Supplementary material. The RNA sequencing data provided in the research are stored in the GEO repository, and the GEO accession number is GSE232387; The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE (56) partner repository with the dataset identifier PXD042073. Further inquiries can be directed to the corresponding author.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37583423", "locator": "sections[26] \"Data availability statement\" paragraph 2", "quote": "The original contributions presented in the study are included in the article/Supplementary material. The RNA sequencing data provided in the research are stored in the GEO repository, and the GEO accession number is GSE232387; The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE (56) partner repository with the dataset identifier PXD042073. Further inquiries can be directed to the corresponding author."}], "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:37583423"], "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. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE1037"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {"fdr_threshold": "ng criteria were set to padj <0"}, "inputs": ["data:geo:GSE1037"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:37583423", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fmed.2023.1203461", "sha256": "sha256:be16eccab6b6a2be60204135fd95bf81d4ef28975ba0db87a9de4c5434d513c9", "bytes": 45121, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fmed.2023.1203461", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC10424445", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE1037", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE1037", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE1037", "version": null, "note": "The original contributions presented in the study are included in the article/Supplementary material. The RNA sequencing data provided in the research are stored in the GEO repository, and the GEO accession number is GSE232387; The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE (56) partner repository with the dataset identifier PXD042073. Further inquiries can be directed to the corresponding author.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The original contributions presented in the study are included in the article/Supplementary material. The RNA sequencing data provided in the research are stored in the GEO repository, and the GEO accession number is GSE232387; The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE (56) partner repository with the dataset identifier PXD042073. 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