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pmid:37874388
A risk score model based on lipid metabolism-related genes could predict response to immunotherapy and prognosis of lung adenocarcinoma: a multi-dataset study and cytological validation.
Yangyang Lei · Boxuan Zhou · Xiangzhi Meng · Mei Liang · Weijian Song · Yicheng Liang · Yushun Gao · Minghui Wang
Discover oncology · 2023 doi:10.1007/s12672-023-00802-3
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Complete file
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However, the relationship between lipid metabolism and prognosis and treatment response of lung adenocarcinoma (LUAD) are still unclear.\nMETHODS: We enrolled seven bulk RNA-sequence datasets (GSE37745, GSE19188, GSE30219, GSE31547, GSE41271, GSE42127, and GSE72094) from the GEO database and one single-cell RNA-sequencing dataset (GSE117570) from the TISCH2 database. Non-negative matrix factorization (NMF) was utilized to construct the risk score model based on lipid score calculated by GSVA algorithm. Phs000452.v3, PMID: 26359337, PMID: 32472114, PRJEB23709 datasets were used to test the response to immunotherapy. Drug sensitivity analysis was assessed according to the GDSC database, and immunotherapy response was evaluated using the Wilcoxon test. Cellular function assays including clone formation, EDU assays and flow cytometry were implemented to explore the phenotype alteration caused by the knockdown of PTDSS1, which is one of key gene in risk score model.\nRESULTS: We analyzed both bulk and single-cell RNA sequencing data to establish and validate a risk score model based on 18 lipid metabolism-related genes with significant impact on prognosis. After divided the patients into two groups according to risk score, we identified differences in lipid-related metabolic processes and a detailed portrait of the immune landscapes of high- and low-risk groups. Moreover, we investigated the potentials of our risk score in predicting response to immunotherapy and drug sensitivity. In addition, we silenced PTDSS1 in LUAD cell lines, and found that the proliferation of the cells was weakened, and the apoptosis of the cells was increased.\nCONCLUSION: Our study highlights the crucial roles of lipid metabolism in LUAD and provides a reliable risk score model, which can aid in predicting prognosis and response to immunotherapy. Furthermore, we investigated the roles of PTDSS1 in LUAD carcinogenesis, which showed that PTDSS1 regulated proliferation and apoptosis of LUAD cells.", "claims": [{"id": "claim-method", "statement": "We performed univariate cox regression on all lipid metabolism-related genes to evaluate their impacts on the prognosis of LUAD patients.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37874388", "locator": "sections[17] \"Prognostic analysis and model construction of lipid-score\" paragraph 2", "quote": "We performed univariate cox regression on all lipid metabolism-related genes to evaluate their impacts on the prognosis of LUAD patients."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Data can be obtained from the corresponding author when required.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37874388", "locator": "sections[29] \"Data availability\" paragraph 2", "quote": "Data can be obtained from the corresponding author when required."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Our study highlights the crucial roles of lipid metabolism in LUAD and provides a reliable risk score model, which can aid in predicting prognosis and response to immunotherapy.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:37874388", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "Our study highlights the crucial roles of lipid metabolism in LUAD and provides a reliable risk score model, which can aid in predicting prognosis and response to immunotherapy."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Our study highlights the crucial roles of lipid metabolism in LUAD and provides a reliable risk score model, which can aid in predicting prognosis and response to immunotherapy.", "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:37874388"], "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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For cell transfection, A549 and NCI-H1975 were transfected with PT", "r cell transfection, A549 and NCI-H1975 were transfected with PTDSS1 knockdown siRNA. We used the 6-w"], "order_basis": "paper_text_order:1274", "id": "assay:2"}, {"role": "data_generation", "definition_id": "scrna_seq", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "unsupported", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["re model. RESULTS: We analyzed both bulk and single-cell RNA sequencing data to establish and validate a risk score"], "order_basis": "paper_text_order:1376", "id": "assay:3"}, {"role": "data_generation", "definition_id": "apoptosis_assay", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["iferation of the cells was weakened, and the apoptosis of the cells was increased. CONCLUSION: Our", "owed that PTDSS1 regulated proliferation and apoptosis of LUAD cells."], "order_basis": "paper_text_order:1985", "id": "assay:4"}, {"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": ["Biosciences (Suzhou, China). The cells were cultured in complete medium, which consisted of 90% DMEM", "es of LUAD were used in this study. Both the A549 and NCI-H1975 were brought from Cyagen Biosc", "phology of the cells. For cell transfection, A549 and NCI-H1975 were transfected with PTDSS1 k"], "order_basis": "paper_text_order:2464", "id": "assay:5"}, {"role": "analysis", "definition_id": "survival_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["cox_ph"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["We performed univariate cox regression on all lipid metabolism-related genes to evaluate their impacts on the prognosis of LUAD patients."], "order_basis": "consumes_earlier_output", "id": "assay:6"}]}