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pmid:36195908
Cancer-associated fibroblast-derived gene signatures predict radiotherapeutic survival in prostate cancer patients.
Ran Zhang · Feng Liu
Journal of translational medicine · 2022 doi:10.1186/s12967-022-03656-5
Paper
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Experiment
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Data
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Analysis
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Execution
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Complete file
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Current clinical indicators are insufficient to accurately assess disease risk and radiotherapy response, emphasizing the urgent need for additional molecular prognostic markers.\nMETHODS: In order to investigate CAF-related genes associated with radiotherapy and construct prognostic CAF-related gene signatures for prostate cancer, we firstly established a radio-resistant prostate CAF cell subline (referred to as CAFR) from Mus-CAF (referred to as CAF) through fractionated irradiation using X-rays. Transcriptome sequencing for CAF and CAFR was conducted, and 2626 CAF-related differentially expressed genes (DEGs) associated with radiotherapy were identified. Human homologous genes of mouse CAF-related DEGs were then obtained.\nRESULTS: Functional enrichment analysis revealed that these CAF-related DEGs were significantly enriched ECM- and immune-related functions and pathways. Based on GSE116918 dataset, 186 CAF-related DEGs were correlated with biochemical recurrence-free survival (BCRFS) of prostate cancer patients, 16 of which were selected to construct a BCRFS-related CAF signature, such as ACPP, THBS2, and KCTD14; 142 CAF-related DEGs were correlated with metastasis-free survival (MFS), 16 of which were used to construct a MFS-related CAF signature, such as HOPX, TMEM132A, and ZNF467. Both Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) datasets confirmed that the two CAF signatures accurately predicted BCRFS and MFS of prostate cancer patients. The risk scores were higher in patients with higher gleason grades and higher clinical T stages. Moreover, the BCRFS-related CAF signature was an independent prognostic factor and a nomogram consisting of BCRFS-related CAF signature and various clinical factors accurately predicted 2-, 3-, and 5-year survival time of prostate cancer patients. Furthermore, the risk score was positively correlated with multiple immune checkpoints.\nCONCLUSIONS: Our established CAF signatures could accurately predict BCRFS and MFS in prostate cancer patients undergoing radiotherapy.", "claims": [{"id": "claim-method", "statement": "To minimize overfitting risk, the least absolute shrinkage and selection operator (LASSO) Cox regression analysis was performed using glmnet package [25] in R.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36195908", "locator": "sections[13] \"Construction of prognostic CAF-related gene signatures\" paragraph 2", "quote": "To minimize overfitting risk, the least absolute shrinkage and selection operator (LASSO) Cox regression analysis was performed using glmnet package [25] in R."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The data used to support the findings of this study are available from the corresponding author upon request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36195908", "locator": "sections[34] \"Availability of data and materials\" paragraph 2", "quote": "The data used to support the findings of this study are available from the corresponding author upon request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Both Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) datasets confirmed that the two CAF signatures accurately predicted BCRFS and MFS of prostate cancer patients.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:36195908", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Both Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) datasets confirmed that the two CAF signatures accurately predicted BCRFS and MFS of prostate cancer patients."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Both Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) datasets confirmed that the two CAF signatures accurately predicted BCRFS and MFS of prostate cancer patients.", "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:36195908"], "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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Human homologous genes of mouse CAF-related DEGs were then obtained. RESULTS"], "order_basis": "paper_text_order:886", "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": 0.77, "evidence": ["previous articles [13, 14]. These cells were cultured in Dulbecco's modified Eagle's medium (DMEM) (S"], "order_basis": "paper_text_order:2512", "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": 0.93, "evidence": ["om. (B) Cell proliferation curve detected by MTT. Figure S3. 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