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pmid:37388902
YAP1 as a Novel Negative Biomarker of Immune Checkpoint Inhibitors for EGFR-Mutant Non-Small-Cell Lung Cancer.
Ling-Chen Li · Xie-Wan Chen · Ling Fang · Chun-Li Jian · Yong-Xin Yu · Xing-Yun Liao · Jian-Guo Sun
Canadian respiratory journal · 2023 doi:10.1155/2023/4689004
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Complete file
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However, its application to epidermal growth factor receptor (EGFR)-mutant NSCLC patients is confronted with drug resistance. This study aimed to clarify the potential role of Yes1-associated transcriptional regulator (YAP1) in ICIs treatment for EGFR-mutant NSCLC population.\nMethods: All the clinical data of NSCLC were downloaded from Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) for GSE11969 and GSE72094. Based on YAP1 expression, all the NSCLC patients including the EGFR-mutant and EGFR-wildtype (WT) patients were divided into two groups, YAP1_High and YAP1_Low. Using cBioPortal, genetic alterations were analyzed for identification of immunogenicity in EGFR-mutant NSCLC. MR analysis was used to analyze the hub gene of EGFR. The infiltration of immune cells and the expression of the identified tumor-associated antigens were identified with TIMER. By graph learning-based dimensionality reduction analysis, the immune landscape was visualized. Moreover, survival analysis was performed to verify the predictive value of YAP1 in ICIs treatment for EGFR-mutant NSCLC population using Ren's research data (NCT03513666).\nResults: YAP1 was a poor prognostic factor of EGFR-mutant NSCLC population rather than lung adenocarcinoma (LUAD) patients. MR analysis revealed that the EGFR gene regulated YAP1 expression. YAP1 was identified as a hub gene closely associated with immunosuppressive microenvironment and poor prognosis in EGFR-mutant NSCLC population in TCGA LUAD. Tumors with YAP1_High showed an immune-\"cold\" and immunosuppressive phenotype, whereas those with YAP1_Low demonstrated an immune-\"hot\" and immunoactive phenotype. More importantly, it was verified that YAP1_High subpopulation had a significantly shorter progression-free survival (PFS) and overall survival (OS) after ICIs treatment in EGFR-mutant NSCLC patients in the clinical trial.\nConclusions: YAP1 mediates immunosuppressive microenvironment and poor prognosis in EGFR-mutant NSCLC population. YAP1 is a novel negative biomarker of ICIs treatment in EGFR-mutant NSCLC population. Clinical Trials. This trial is registered with NCT03513666.", "claims": [{"id": "claim-method", "statement": "Kaplan–Meier analysis of OS and PFS) was performed using Survminer [18] (R package). We calculated the hazard ratio (HR) and log-rank P value of the 95% confidence interval.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37388902", "locator": "sections[6] \"2.4. Survival Analysis\" paragraph 2", "quote": "Kaplan–Meier analysis of OS and PFS) was performed using Survminer [18] (R package). We calculated the hazard ratio (HR) and log-rank P value of the 95% confidence interval."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets used in the present study are obtained from the corresponding author upon reasonable request. Our data were obtained from Gene Expression Omnibus (GEO), TCGA LUAD and a phase-II, multicenter, open-label trial from Ren's research (NCT03513666).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37388902", "locator": "sections[21] \"Data Availability\" paragraph 2", "quote": "The datasets used in the present study are obtained from the corresponding author upon reasonable request. Our data were obtained from Gene Expression Omnibus (GEO), TCGA LUAD and a phase-II, multicenter, open-label trial from Ren's research (NCT03513666)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "YAP1 was associated with poorer outcomes and an immunosuppressive tumor microenvironment in EGFR-mutant NSCLC, and high YAP1 expression was associated with shorter survival after immune checkpoint inhibitor treatment.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:37388902", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "YAP1 mediates immunosuppressive microenvironment and poor prognosis in EGFR-mutant NSCLC population. YAP1 is a novel negative biomarker of ICIs treatment in EGFR-mutant NSCLC population."}, {"asset": "source:pmid:37388902", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "More importantly, it was verified that YAP1_High subpopulation had a significantly shorter progression-free survival (PFS) and overall survival (OS) after ICIs treatment in EGFR-mutant NSCLC patients in the clinical trial."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "YAP1 was associated with poorer outcomes and an immunosuppressive tumor microenvironment in EGFR-mutant NSCLC, and high YAP1 expression was associated with shorter survival after immune checkpoint inhibitor treatment.", "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:37388902"], "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:GSE11969"], "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": {"hazard_ratio": "survival analysis with hazard ratio and log-rank P value ca", "p_value": "zard ratio and log-rank P value calculation"}, "inputs": ["data:geo:GSE11969"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:37388902", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1155/2023/4689004", "sha256": "sha256:d00f5b29fe19da7c95598a7440821d48b1787621e25e5edaf8cbf1b6189cbd5a", "bytes": 39135, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1155/2023/4689004", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC10307059", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE11969", "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=GSE11969", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE11969", "version": null, "note": "The datasets used in the present study are obtained from the corresponding author upon reasonable request. 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