Generation of novel lipid metabolism-based signatures to predict prognosis and immunotherapy response for colorectal adenocarcinoma.

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This study aimed to generate lipid metabolism-based signatures to predict prognosis, immunotherapy and chemotherapy response for colorectal adenocarcinoma (COAD). Transcriptome data and clinical information of COAD patients were collected from the cancer genome atlas (TCGA) database. The expression of EMT-, stem cell-, and IC-related genes were assessed between COAD and control samples. Modules and genes correlated EMT, ICs and stemness signatures were identified through weighted gene co-expression network analysis (WGCNA). Prognostic signatures were generated and then the distribution of risk genes was evaluated using single-cell RNA sequencing (scRNA-seq) data from GSE132465 dataset. COAD patients exhibited increased EMT score and stemness along with decreased ICs. Next, 12 hub genes (PIK3CG, ALOX5AP, PIK3R5, TNFAIP8L2, DPEP2, PIK3CD, PIK3R6, GGT5, ELOVL4, PTGIS, CYP7B1 and PRKD1) were found within green and yellow modules correlated with EMT, stemness and ICs. Lipid metabolism-based prognostic signatures were generated based on PIK3CG, GGT5 and PTGIS. Patients with high-risk group had poor prognosis, elevated ESTIMATEScore and StromalScore, 100% mutation rate and higher TIDE score. Samples in low-risk group had more immunogenicity on ICIs. Notably, PIK3CG was expressed in B cells, while GGT5 and PTGIS were expressed in stromal cells. This study generates lipid metabolism-based signatures correlated with EMT, stemness and ICs for predicting prognosis of COAD, and provides potential therapeutic targets for immunotherapy in COAD.", "claims": [{"id": "claim-method", "statement": "Based on 742 lipid metabolism-related genes, WGCNA was performed to identify co-expression modules.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39060344", "locator": "sections[4] \"Identification of co-expression modules and hub genes using WGCNA\" paragraph 2", "quote": "Based on 742 lipid metabolism-related genes, WGCNA was performed to identify co-expression modules."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39060344", "locator": "sections[26] \"Data availability\" paragraph 2", "quote": "The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Weighted gene co-expression network analysis (WGCNA) was performed on 742 lipid metabolism-related genes to identify co-expression modules and genes correlated with EMT, immune checkpoints, and stemness signatures.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:39060344", "locator": "sections[4] \"Identification of co-expression modules and hub genes using WGCNA\" paragraph 2", "quote": "Based on 742 lipid metabolism-related genes, WGCNA was performed to identify co-expression modules."}, {"asset": "source:pmid:39060344", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Transcriptome data and clinical information of COAD patients were collected from the cancer genome atlas (TCGA) database."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Weighted gene co-expression network analysis (WGCNA) was performed on 742 lipid metabolism-related genes to identify co-expression modules and genes correlated with EMT, immune checkpoints, and stemness signatures.", "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:39060344"], "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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