Single-Cell RNA-Seq Reveals the Promoting Role of Ferroptosis Tendency During Lung Adenocarcinoma EMT Progression.

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We used single-cell RNA sequencing to investigate the regulatory connection between EMT and ferroptosis tendency in LUAD epithelial cells. We used Seurat to construct the expression matrix using the GEO dataset GSE131907 and extract epithelial cells. We found a positive correlation between the trends of EMT and ferroptosis tendency. Then we used SCENIC to analyze differentially activated transcription factors and constructed a molecular regulatory directed network by causal inference. Some ferroptosis markers (GPX4, SCP2, CAV1) were found to have strong regulatory effects on EMT. Cell communication networks were constructed by iTALK and implied that Ferro_High_EMT_High cells have a higher expression of SDC1, SDC4, and activation of LGALS9-HARVCR2 pathways. By deconvolution of bulk sequencing, the results of CIBERSORTx showed that the co-occurrence of ferroptosis tendency and EMT may lead to tumor metastasis and non-response to immunotherapy. Our findings showed there is a strong correlation between ferroptosis tendency and EMT. Ferroptosis may have a promotive effect on EMT. High propensities of ferroptosis and EMT may lead to poor prognosis and non-response to immunotherapy.", "claims": [{"id": "claim-method", "statement": "Since the tumor tissues come from different metastatic sites, we put the research center on EMT, using 23 EMT up-regulated and 3 EMT down-regulated gene sets obtained from MSigDB to perform ssGSEA on all ECs (Subramanian et al., 2005).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35127731", "locator": "sections[3] \"EMT and Ferroptosis in mLN are Positively Correlated\" paragraph 4", "quote": "Since the tumor tissues come from different metastatic sites, we put the research center on EMT, using 23 EMT up-regulated and 3 EMT down-regulated gene sets obtained from MSigDB to perform ssGSEA on all ECs (Subramanian et al., 2005)."}], "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 authors.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35127731", "locator": "sections[18] \"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 authors."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The paper found a strong positive correlation between ferroptosis tendency and EMT and proposed that ferroptosis tendency promotes EMT.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:35127731", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Our findings showed there is a strong correlation between ferroptosis tendency and EMT."}, {"asset": "source:pmid:35127731", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Ferroptosis may have a promotive effect on EMT."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The paper found a strong positive correlation between ferroptosis tendency and EMT and proposed that ferroptosis tendency promotes EMT.", "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:35127731"], "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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