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pmid:32236130
Transcriptome analysis reveals gender-specific differences in overall metabolic response of male and female patients in lung adenocarcinoma.
Ya Li · Cheng-Lu He · Wen-Xing Li · Rui-Xian Zhang · Yong Duan
PloS one · 2020 doi:10.1371/journal.pone.0230796
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Experiment
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Complete file
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The present study aimed to explore differences in the global metabolic response between male and female patients in LUAD and to identify the metabolic genes associated with lung cancer susceptibility.\nMETHODS: Transcriptome and clinical LUAD data were acquired from The Cancer Genome Atlas (TCGA) database. Information on metabolic genes and metabolic subsystems were collected from the Recon3D human metabolic model. Two validation datasets (GSE68465 and GSE72094) were downloaded from the Gene Expression Omnibus (GEO) database. Differential expression analysis, gene set enrichment analysis and protein-protein interaction networks were used to identified key metabolic pathways and genes. Functional experiments were used to verify the effects of genes on proliferation, migration, and invasion in lung cancer cells in vitro.\nRESULTS: Samples of tumors and adjacent non-tumor tissue from both male and female patients exhibited distinct global patterns of gene expression. In addition, we found large differences in methionine and cysteine metabolism, pyruvate metabolism, cholesterol metabolism, nicotinamide adenine dinucleotide (NAD) metabolism, and nuclear transport between male and female LUAD patients. We identified 34 metabolic genes associated with lung cancer susceptibility in males and 15 in females. Most of the metabolic cancer-susceptibility genes had high prediction accuracy for lung cancer (AUC > 0.9). Furthermore, both bioinformatics analysis and experimental results showed that TAOK2 was down-regulated and ASAH1 was up-regulated in male tumor tissue and female tumor tissue in LUAD. Functional experiments showed that inhibiting ASAH1 suppressed the proliferation, migration, and invasion of lung cancer cells.\nCONCLUSIONS: Metabolic cancer-susceptibility genes may be used alone or in combination as diagnostic markers for LUAD. Further studies are required to elucidate the functions of these genes in LUAD.", "claims": [{"id": "claim-method", "statement": "The LUAD transcriptomes and clinical data were downloaded from the Genomic Data Commons (GDC) Data Portal (https://portal.gdc.cancer.gov/). 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Kaplan-Meier survival curves were used to express differences between high and low expression levels of each metabolic gene among groups in relation to the prognosis of the patient."}}, {"id": "method-2", "family": "group_comparison", "specific": "wilcoxon", "label": "Group comparison", "dsl_operations": [], "missing_operations": ["group_comparison_wilcoxon"], "expressible": false, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 0.8, "band": "high", "quote": "Wilcoxon"}}, {"id": "method-3", "family": "survival_analysis", "specific": "cox_proportional_hazards", "label": "Survival analysis", "dsl_operations": ["cox_ph"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["time_to_event_with_censoring"], "evidence": {"score": 0.8, "band": "high", "quote": "Cox proportional hazards"}}, {"id": "method-4", "family": "network_analysis", "specific": "ppi_network", "label": "Network / pathway analysis", "dsl_operations": ["build_graph", "centrality_scores", "pathway_enrich"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["edge_list"], "evidence": {"score": 0.7, "band": "medium", "quote": "protein-protein interaction"}}, {"id": "method-5", "family": "contingency_analysis", "specific": "chi_square", "label": "Categorical (contingency table) analysis", "dsl_operations": ["chi_square_test"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["categorical_cross_tabulation"], "evidence": {"score": 0.8, "band": "high", "quote": "χ2"}}], "targets": [], "gaps": ["method.reader_differs_from_extractor"]}, "capability": {"state": "complete", "requirements": [{"capability_id": "capability:computational_analysis", "label": "Computational analysis platform", "assay_families": ["meta_analysis", "machine_learning", "survival_analysis", "statistical_regression", "pca", "molecular_docking", "network_analysis", "differential_expression", "gwas"], "availability_state": "owned", "tier_unlocked": "R1", "candidate": "Automated Assays Laravel application and simulated adapters"}], "gaps": []}, "readiness": {"state": "complete", "tier": "R1", "blocking_axis": "none", "blocked_on": "nothing:replicable_now", "axes": {"method": {"tier": "R1", "expressible": true, "required_operations": ["survival_km"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: kaplan_meier."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. 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Cells were transfected with knockdown plasmid (siASAH1#1 and siASAH"], "order_basis": "paper_text_order:5599", "id": "assay:1"}, {"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["University, A549 and XWLC-05 cells were all cultured in RPMI-1640 medium (Hyclone, USA) supplemented", "CC and cultured following standard protocol. A549 and XWLC-05 lung adenocarcinoma cancer cell", "linical Cancer, Kunming Medicine University, A549 and XWLC-05 cells were all cultured in RPMI-", "in lung cancer cells was evaluated. Briefly, A549 and XWLC-05 cells with high ASAH1 expression"], "order_basis": "paper_text_order:5993", "id": "assay:2"}, {"role": "data_generation", "definition_id": "apoptosis_assay", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["ank vector (siCtrl or exCtrl), respectively. CCK-8 assay and invasion assay were performed to i", "adenocarcinoma cancer cells in vitro.(A) The CCK-8 assay results showing the proliferation abil"], "order_basis": "paper_text_order:7198", "id": "assay:3"}, {"role": "analysis", "definition_id": "survival_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["survival_km"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["The LUAD transcriptomes and clinical data were downloaded from the Genomic Data Commons (GDC) Data Portal (https://portal.gdc.cancer.gov/). Kaplan-Meier survival curves were used to express differences between high and low expression levels of each metabolic gene among groups in relation to the prognosis of the patient."], "order_basis": "consumes_earlier_output", "id": "assay:4"}]}