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pmid:36778142

Construction and validation of a fatty acid metabolism-related gene signature for predicting prognosis and therapeutic response in patients with prostate cancer.

Hongjun Zhao · Tong Wu · Zehao Luo · Qinyao Huang · Sihua Zhu · Chunling Li · Zubing Zhang · Jiahao Zhang · Jianwen Zeng · Yuying Zhang

PeerJ · 2023 doi:10.7717/peerj.14854

Paper

complete

Experiment

complete

Data

partial

Analysis

partial

Execution

absent

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Construction and validation of a fatty acid metabolism-related gene signature for predicting prognosis and therapeutic response in patients with prostate cancer.
doi
10.7717/peerj.14854
pmid
36778142
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[0]
Hongjun Zhao
[1]
Tong Wu
[2]
Zehao Luo
[3]
Qinyao Huang
[4]
Sihua Zhu
[5]
Chunling Li
[6]
Zubing Zhang
[7]
Jiahao Zhang
[8]
Jianwen Zeng
[9]
Yuying Zhang
journal
PeerJ
year
2023
abstract
Background: Reprogramming of fatty acid metabolism is a newly-identified hallmark of malignancy. However, no studies have systematically investigated the fatty acid metabolism related-gene set in prostate cancer (PCa). Methods: A cohort of 381 patients with gene expression and clinical data from The Cancer Genome Atlas was used as the training set, while another cohort of 90 patients with PCa from GEO (GSE70769) was used as the validation set. Differentially expressed fatty acid metabolism-related genes were subjected to least absolute shrinkage and selection operator (LASSO)-Cox regression to establish a fatty acid metabolism-related risk score. Associations between the risk score and clinical characteristics, immune cell infiltration, tumor mutation burden (TMB), tumor immune dysfunction and exclusion (TIDE) score, and response to chemotherapy were analyzed. Finally, the expression level of genes included in the model was validated using real-time PCR. Results: A prognostic risk model based on five fatty acid metabolism related genes (ALDH1A1, CPT1B, CA2, CROT, and NUDT19) were constructed. Tumors with higher risk score were associated with larger tumor size, lymph node involvement, higher Gleason score, and poorer biochemical recurrence (BCR)-free survival. Furthermore, the high- and low-risk tumors exhibited distinct immune cell infiltration features and immune-related pathway activation. High-risk tumors were associated with favorable response to immunotherapy as indicated by high TMB and low TIDE score, but poor response to bicalutamide and docetaxel chemotherapy. Conclusion: This study established a fatty acid metabolism-related gene signature which was predictive of BCR and response to chemotherapy and immunotherapy, providing a novel therapeutic biomarker for PCa.
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Differentially expressed fatty acid metabolism-related genes were subjected to least absolute shrinkage and selection operator (LASSO)-Cox regression to establish a fatty acid metabolism-related risk score.
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The following information was supplied regarding data availability:The GDC TCGA Prostate Cancer (PRAD) data is available at UCSC Xena: https://xena.ucsc.edu/welcome-to-ucsc-xena.The data is available at NCBI GEO: GSE70769.
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The following information was supplied regarding data availability:The GDC TCGA Prostate Cancer (PRAD) data is available at UCSC Xena: https://xena.ucsc.edu/welcome-to-ucsc-xena.The data is available at NCBI GEO: GSE70769.
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This study established a fatty acid metabolism-related gene signature which was predictive of BCR and response to chemotherapy and immunotherapy, providing a novel therapeutic biomarker for PCa.
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This study established a fatty acid metabolism-related gene signature which was predictive of BCR and response to chemotherapy and immunotherapy, providing a novel therapeutic biomarker for PCa.
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This study established a fatty acid metabolism-related gene signature which was predictive of BCR and response to chemotherapy and immunotherapy, providing a novel therapeutic biomarker for PCa.
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The following information was supplied regarding data availability:The GDC TCGA Prostate Cancer (PRAD) data is available at UCSC Xena: https://xena.ucsc.edu/welcome-to-ucsc-xena.The data is available at NCBI GEO: GSE70769.
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Complete file
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However, no studies have systematically investigated the fatty acid metabolism related-gene set in prostate cancer (PCa).\nMethods: A cohort of 381 patients with gene expression and clinical data from The Cancer Genome Atlas was used as the training set, while another cohort of 90 patients with PCa from GEO (GSE70769) was used as the validation set. Differentially expressed fatty acid metabolism-related genes were subjected to least absolute shrinkage and selection operator (LASSO)-Cox regression to establish a fatty acid metabolism-related risk score. Associations between the risk score and clinical characteristics, immune cell infiltration, tumor mutation burden (TMB), tumor immune dysfunction and exclusion (TIDE) score, and response to chemotherapy were analyzed. Finally, the expression level of genes included in the model was validated using real-time PCR.\nResults: A prognostic risk model based on five fatty acid metabolism related genes (ALDH1A1, CPT1B, CA2, CROT, and NUDT19) were constructed. Tumors with higher risk score were associated with larger tumor size, lymph node involvement, higher Gleason score, and poorer biochemical recurrence (BCR)-free survival. Furthermore, the high- and low-risk tumors exhibited distinct immune cell infiltration features and immune-related pathway activation. High-risk tumors were associated with favorable response to immunotherapy as indicated by high TMB and low TIDE score, but poor response to bicalutamide and docetaxel chemotherapy.\nConclusion: This study established a fatty acid metabolism-related gene signature which was predictive of BCR and response to chemotherapy and immunotherapy, providing a novel therapeutic biomarker for PCa.", "claims": [{"id": "claim-method", "statement": "Differentially expressed fatty acid metabolism-related genes were subjected to least absolute shrinkage and selection operator (LASSO)-Cox regression to establish a fatty acid metabolism-related risk score.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36778142", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "Differentially expressed fatty acid metabolism-related genes were subjected to least absolute shrinkage and selection operator (LASSO)-Cox regression to establish a fatty acid metabolism-related risk score."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The following information was supplied regarding data availability:The GDC TCGA Prostate Cancer (PRAD) data is available at UCSC Xena: https://xena.ucsc.edu/welcome-to-ucsc-xena.The data is available at NCBI GEO: GSE70769.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36778142", "locator": "sections[22] \"Additional Information and Declarations\" paragraph 4", "quote": "The following information was supplied regarding data availability:The GDC TCGA Prostate Cancer (PRAD) data is available at UCSC Xena: https://xena.ucsc.edu/welcome-to-ucsc-xena.The data is available at NCBI GEO: GSE70769."}], "state": "complete"}, {"id": "claim-target-result", "statement": "This study established a fatty acid metabolism-related gene signature which was predictive of BCR and response to chemotherapy and immunotherapy, providing a novel therapeutic biomarker for PCa.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:36778142", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "This study established a fatty acid metabolism-related gene signature which was predictive of BCR and response to chemotherapy and immunotherapy, providing a novel therapeutic biomarker for PCa."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "This study established a fatty acid metabolism-related gene signature which was predictive of BCR and response to chemotherapy and immunotherapy, providing a novel therapeutic biomarker for PCa.", "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:36778142"], "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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