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pmid:35982906
Development and Validation of a DNA Methylation-related Classifier of Circulating Tumour Cells to Predict Prognosis and to provide a therapeutic strategy in Lung Adenocarcinoma.
Xuyu Gu · Xianting Huang · Xiuxiu Zhang · Cailian Wang
International journal of biological sciences · 2022 doi:10.7150/ijbs.75284
Paper
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Experiment
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Data
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Analysis
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Execution
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Complete file
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Studies have shown that abnormal DNA methylation in circulating tumor cells (CTCs) is associated with tumour metastasis. Based on the genes expressed in CTCs that play an important role in DNA methylation, we hope to build a risk model to predict prognosis and provide a therapeutic strategy in LUAD. Methods: The CTC sequencing data for LUAD were obtained from GSE74639, which contains 10 CTC samples and 6 primary tumour samples. To carefully assess the clinical value, functional status, involvement of the tumor microenvironment (TME) based on the risk model, and genetic variants based on based on data from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO), a reliable risk model was successfully built. Results: Three differentially methylated genes (DMGs) of CTCs for LUAD, including mitochondrial ribosomal protein L51 (MRPL51), STE20-like kinase (SLK), and protein regulator of cytokinesis 1(PRC1), were effectively used to construct a risk model. Both the training and validation cohorts' stability and accuracy of the risk model were evaluated. Each patient in the TCGA-LUAD cohort received a risk score, and based on the median score, they were divided into high- and low-risk groups. The tumors in the high-risk group in this study were classified as \"cold\" and immunosuppressed, which may be linked to a poor prognosis. The tumors in the low-risk group, however, were deemed \"hot\" and had immune hyperfunction linked to a positive prognosis. Additionally, patients in the low-risk group showed greater sensitivity to immunotherapy than those in the high-risk group. Conclusions: Based on DMGs of CTCs from LUAD, we successfully developed a predictive risk model and discovered differences in biological function, TME, genetic variation, and clinical outcomes between those at high and low risk group.", "claims": [{"id": "claim-method", "statement": "Additionally, by examining the correlation between gene expression and methylation level using R<0 and p<0.05 as criteria, differential methylation-driven genes (DMGs) were found.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35982906", "locator": "sections[4] \"Screening of methylation-driven genes\" paragraph 2", "quote": "Additionally, by examining the correlation between gene expression and methylation level using R<0 and p<0.05 as criteria, differential methylation-driven genes (DMGs) were found."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35982906", "locator": "sections[24] \"Data Availability Statement\" paragraph 2", "quote": "The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Three differentially methylated genes (DMGs) of CTCs for LUAD, including mitochondrial ribosomal protein L51 (MRPL51), STE20-like kinase (SLK), and protein regulator of cytokinesis 1(PRC1), were effectively used to construct a risk model.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:35982906", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Three differentially methylated genes (DMGs) of CTCs for LUAD, including mitochondrial ribosomal protein L51 (MRPL51), STE20-like kinase (SLK), and protein regulator of cytokinesis 1(PRC1), were effectively used to construct a risk model."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "Three differentially methylated genes (DMGs) of CTCs for LUAD, including mitochondrial ribosomal protein L51 (MRPL51), STE20-like kinase (SLK), and protein regulator of cytokinesis 1(PRC1), were effectively used to construct a risk model.", "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:35982906"], "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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