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pmid:37483592

Insight of a lipid metabolism prognostic model to identify immune landscape and potential target for retroperitoneal liposarcoma.

Zhenyu Wang · Ping Tao · Peidang Fan · Jiongyuan Wang · Tao Rong · Yingyong Hou · Yuhong Zhou · Weiqi Lu · Liang Hong · Lijie Ma · Yong Zhang · Hanxing Tong

Frontiers in immunology · 2023 doi:10.3389/fimmu.2023.1209396

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Insight of a lipid metabolism prognostic model to identify immune landscape and potential target for retroperitoneal liposarcoma.
doi
10.3389/fimmu.2023.1209396
pmid
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Zhenyu Wang
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Ping Tao
[2]
Peidang Fan
[3]
Jiongyuan Wang
[4]
Tao Rong
[5]
Yingyong Hou
[6]
Yuhong Zhou
[7]
Weiqi Lu
[8]
Liang Hong
[9]
Lijie Ma
[10]
Yong Zhang
[11]
Hanxing Tong
journal
Frontiers in immunology
year
2023
abstract
Introduction: The exploration of lipid metabolism dysregulation may provide novel perspectives for retroperitoneal liposarcoma (RPLS). In our study, we aimed to investigate potential targets and facilitate further understanding of immune landscape in RPLS, through lipid metabolism-associated genes (LMAGs) based prognostic model. Methods: Gene expression profiles and corresponding clinical information of 234 cases were enrolled from two public databases and the largest retroperitoneal tumor research center of East China, including cohort-TCGA (n=58), cohort-GSE30929 (n=92), cohort-FD (n=50), cohort-scRNA-seq (n=4) and cohort-validation (n=30). Consensus clustering analysis was performed to identify lipid metabolism-associated molecular subtypes (LMSs). A prognostic risk model containing 13 LMAGs was established using LASSO algorithm and multivariate Cox analysis in cohort-TCGA. ESTIMATE, CIBERSORT, XCELL and MCP analyses were performed to visualize the immune landscape. WGCNA was used to identify three hub genes among the 13 model LMAGs, and preliminarily validated in both cohort-GSE30929 and cohort-FD. Moreover, TIMER was used to visualize the correlation between antigen-presenting cells and potential targets. Finally, single-cell RNA-sequencing (scRNA-seq) analysis of four RPLS and multiplexed immunohistochemistry (mIHC) were performed in cohort-validation to validate the discoveries of bioinformatics analysis. Results: LMS1 and LMS2 were characterized as immune-infiltrated and -excluded tumors, with significant differences in molecular features and clinical prognosis, respectively. Elongation of very long chain fatty acids protein 2 (ELOVL2), the enzyme that catalyzed the elongation of long chain fatty acids, involved in the maintenance of lipid metabolism and cellular homeostasis in normal cells, was identified and negatively correlated with antigen-presenting cells and identified as a potential target in RPLS. Furthermore, ELOVL2 was enriched in LMS2 with significantly lower immunoscore and unfavorable prognosis. Finally, a high-resolution dissection through scRNA-seq was performed in four RPLS, revealing the entire tumor ecosystem and validated previous findings. Discussion: The LMS subgroups and risk model based on LMAGs proposed in our study were both promising prognostic classifications for RPLS. ELOVL2 is a potential target linking lipid metabolism to immune regulations against RPLS, specifically for patients with LMS2 tumors.
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24 LMAGs were found to be considerably linked to the OS of patients through LASSO regression analysis ( Figures 4A, B ), 13 of which were tested and selected for the risk score model from multivariate Cox analysis ( Supplementary Figure 4A ).
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24 LMAGs were found to be considerably linked to the OS of patients through LASSO regression analysis ( Figures 4A, B ), 13 of which were tested and selected for the risk score model from multivariate Cox analysis ( Supplementary Figure 4A ).
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Specifically, this OS related model indicated a great accuracy with AUC values of 0.94 in 1 year, 0.97 in 3 years and 0.97 in 5 years ( Figure 4E ).
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A-seq) analysis of four RPLS and multiplexed immunohistochemistry (mIHC) were performed in cohort-validation t
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24 LMAGs were found to be considerably linked to the OS of patients through LASSO regression analysis ( Figures 4A, B ), 13 of which were tested and selected for the risk score model from multivariate Cox analysis ( Supplementary Figure 4A ).
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In our study, we aimed to investigate potential targets and facilitate further understanding of immune landscape in RPLS, through lipid metabolism-associated genes (LMAGs) based prognostic model.\nMethods: Gene expression profiles and corresponding clinical information of 234 cases were enrolled from two public databases and the largest retroperitoneal tumor research center of East China, including cohort-TCGA (n=58), cohort-GSE30929 (n=92), cohort-FD (n=50), cohort-scRNA-seq (n=4) and cohort-validation (n=30). Consensus clustering analysis was performed to identify lipid metabolism-associated molecular subtypes (LMSs). A prognostic risk model containing 13 LMAGs was established using LASSO algorithm and multivariate Cox analysis in cohort-TCGA. ESTIMATE, CIBERSORT, XCELL and MCP analyses were performed to visualize the immune landscape. WGCNA was used to identify three hub genes among the 13 model LMAGs, and preliminarily validated in both cohort-GSE30929 and cohort-FD. Moreover, TIMER was used to visualize the correlation between antigen-presenting cells and potential targets. Finally, single-cell RNA-sequencing (scRNA-seq) analysis of four RPLS and multiplexed immunohistochemistry (mIHC) were performed in cohort-validation to validate the discoveries of bioinformatics analysis.\nResults: LMS1 and LMS2 were characterized as immune-infiltrated and -excluded tumors, with significant differences in molecular features and clinical prognosis, respectively. Elongation of very long chain fatty acids protein 2 (ELOVL2), the enzyme that catalyzed the elongation of long chain fatty acids, involved in the maintenance of lipid metabolism and cellular homeostasis in normal cells, was identified and negatively correlated with antigen-presenting cells and identified as a potential target in RPLS. Furthermore, ELOVL2 was enriched in LMS2 with significantly lower immunoscore and unfavorable prognosis. Finally, a high-resolution dissection through scRNA-seq was performed in four RPLS, revealing the entire tumor ecosystem and validated previous findings.\nDiscussion: The LMS subgroups and risk model based on LMAGs proposed in our study were both promising prognostic classifications for RPLS. ELOVL2 is a potential target linking lipid metabolism to immune regulations against RPLS, specifically for patients with LMS2 tumors.", "claims": [{"id": "claim-method", "statement": "24 LMAGs were found to be considerably linked to the OS of patients through LASSO regression analysis ( Figures 4A, B ), 13 of which were tested and selected for the risk score model from multivariate Cox analysis ( Supplementary Figure 4A ).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37483592", "locator": "sections[25] \"Development of survival and relapse risk models and nomograms based on LMAGs\" paragraph 3", "quote": "24 LMAGs were found to be considerably linked to the OS of patients through LASSO regression analysis ( Figures 4A, B ), 13 of which were tested and selected for the risk score model from multivariate Cox analysis ( Supplementary Figure 4A )."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The transcriptome data presented in the study are deposited in the Sequence Read Archive (SRA) repository, accession number PRJNA987378.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37483592", "locator": "sections[29] \"Data availability statement\" paragraph 2", "quote": "The transcriptome data presented in the study are deposited in the Sequence Read Archive (SRA) repository, accession number PRJNA987378."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Specifically, this OS related model indicated a great accuracy with AUC values of 0.94 in 1 year, 0.97 in 3 years and 0.97 in 5 years ( Figure 4E ).", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:37483592", "locator": "sections[25] \"Development of survival and relapse risk models and nomograms based on LMAGs\" paragraph 3", "quote": "Specifically, this OS related model indicated a great accuracy with AUC values of 0.94 in 1 year, 0.97 in 3 years and 0.97 in 5 years ( Figure 4E )."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Specifically, this OS related model indicated a great accuracy with AUC values of 0.94 in 1 year, 0.97 in 3 years and 0.97 in 5 years ( Figure 4E ).", "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:37483592"], "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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