Development of cancer-associated fibroblast-related gene signature for predicting the survival and immunotherapy response in lung adenocarcinoma.

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The weighted gene correlation network analysis was utilized to identify the hub modules related to immune/stromal cells. Then, univariate, LASSO, and multivariate Cox regression analyses were employed to develop a predictive signature based on genes of the hub module. Moreover, the association between the predictive signature and immunotherapy response was also investigated. As a result, seven genes (FGF10, SERINE2, LSAMP, STXBP5, PDE5A, GLI2, FRMD6) were screened to develop the cancer associated fibroblasts (CAFs)-related risk signature (CAFRS). LUAD patients with high-risk score underwent shortened Overall survival (OS). A strong correlation was found between CAFRS and immune infiltrations/functions. The gene set variation analysis showed that G2/M checkpoint, epithelial-mesenchymal transition, hypoxia, glycolysis, and PI3K-Akt-mTOR pathways were greatly enriched in the high-risk subgroup. Moreover, patients with higher risk score were less likely to respond to immunotherapy. A nomogram based on CAFRS and Stage presented a stronger predictive performance for OS than the single indicator. In conclusion, the CAFRS exhibited a potent predictive value for OS and immunotherapy response in LUAD.", "claims": [{"id": "claim-method", "statement": "The R package of WGCNA was employed to construct the weight co-expression network based on the gene expression matrix of TCGA-LUAD.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37280069", "locator": "sections[5] \"Selection of hub modules related to immune or stromal cells\" paragraph 2", "quote": "The R package of WGCNA was employed to construct the weight co-expression network based on the gene expression matrix of TCGA-LUAD."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The transcriptome and somatic mutational profiles and clinical data of LUAD were extracted from TCGA-GDC (https://portal.gdc.cancer.gov/).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37280069", "locator": "sections[3] \"Data acquisition and preprocessing\" paragraph 2", "quote": "The transcriptome and somatic mutational profiles and clinical data of LUAD were extracted from TCGA-GDC (https://portal.gdc.cancer.gov/)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Finally, we chose the pink module (closely related to CAFs) containing 580 genes for the subsequent predictive model construction due to the highest correlation coefficient (R = 0.82, P <0.001) with CAFs (Figure 1E).", "kind": "quantitative", "target": {"value": 0.82, "unit": "correlation coefficient", "tolerance": null, "source": "Finally, we chose the pink module (closely related to CAFs) containing 580 genes for the subsequent predictive model construction due to the highest correlation coefficient (R = 0.82, P <0.001) with CAFs (Figure 1E)."}, "evidence": [{"asset": "source:pmid:37280069", "locator": "sections[13] \"Construction of the weighted co-expression network and identification of the hub module\" paragraph 2", "quote": "Finally, we chose the pink module (closely related to CAFs) containing 580 genes for the subsequent predictive model construction due to the highest correlation coefficient (R = 0.82, P <0.001) with CAFs (Figure 1E)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Finally, we chose the pink module (closely related to CAFs) containing 580 genes for the subsequent predictive model construction due to the highest correlation coefficient (R = 0.82, P <0.001) with CAFs (Figure 1E).", "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:37280069"], "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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