By integrating single-cell RNA-seq and bulk RNA-seq in sphingolipid metabolism, CACYBP was identified as a potential therapeutic target in lung adenocarcinoma
BackgroundLung adenocarcinoma (LUAD) is a heterogeneous disease with a dismal prognosis for advanced tumors. Immune-associated cells in the microenvironment substantially impact LUAD formation and progression, which has gained increased attention in recent decades. Sphingolipids have a profound impa...
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| Format: | Article |
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Frontiers Media S.A.
2023-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1115272/full |
| _version_ | 1828053057863155712 |
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| author | Pengpeng Zhang Shengbin Pei Zeitian Gong Yanlong Feng Xiao Zhang Fang Yang Wei Wang |
| author_facet | Pengpeng Zhang Shengbin Pei Zeitian Gong Yanlong Feng Xiao Zhang Fang Yang Wei Wang |
| author_sort | Pengpeng Zhang |
| collection | DOAJ |
| description | BackgroundLung adenocarcinoma (LUAD) is a heterogeneous disease with a dismal prognosis for advanced tumors. Immune-associated cells in the microenvironment substantially impact LUAD formation and progression, which has gained increased attention in recent decades. Sphingolipids have a profound impact on tumor formation and immune infiltration. However, few researchers have focused on the utilization of sphingolipid variables in the prediction of LUAD prognosis. The goal of this work was to identify the major sphingolipid-related genes (SRGs) in LUAD and develop a valid prognostic model based on SRGs.MethodsThe most significant genes for sphingolipid metabolism (SM) were identified using the AUCell and WGCNA algorithms in conjunction with single-cell and bulk RNA-seq. LASSO and COX regression analysis was used to develop risk models, and patients were divided into high-and low-risk categories. External nine provided cohorts evaluated the correctness of the models. Differences in immune infiltration, mutation landscape, pathway enrichment, immune checkpoint expression, and immunotherapy were also further investigated in distinct subgroups. Finally, cell function assay was used to verify the role of CACYBP in LUAD cells.ResultsA total of 334 genes were selected as being most linked with SM activity for further investigation, and a risk model consisting of 11 genes was established using lasso and cox regression. According to the median risk value, patients were split into high- and low-risk groups, and the high-risk group had a worse prognosis. The low-risk group had more immune cell infiltration and higher expression of immune checkpoints, which illustrated that the low-risk group was more likely to benefit from immunotherapy. It was verified that CACYBP could increase the ability of LUAD cells to proliferate, invade, and migrate.ConclusionThe eleven-gene signature identified in this research may help physicians create individualized care plans for LUAD patients. CACYBP may be a new therapeutic target for patients with advanced LUAD. |
| first_indexed | 2024-04-10T20:01:48Z |
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| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-10T20:01:48Z |
| publishDate | 2023-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-bd3b6ce533b0494cb2e73db5a3b48e042023-01-27T04:38:54ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-01-011410.3389/fimmu.2023.11152721115272By integrating single-cell RNA-seq and bulk RNA-seq in sphingolipid metabolism, CACYBP was identified as a potential therapeutic target in lung adenocarcinomaPengpeng Zhang0Shengbin Pei1Zeitian Gong2Yanlong Feng3Xiao Zhang4Fang Yang5Wei Wang6Department of Thoracic Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of Breast Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of Thoracic Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of Thoracic Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of Thoracic Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of Ophthalmology, Charité – Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, GermanyDepartment of Thoracic Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaBackgroundLung adenocarcinoma (LUAD) is a heterogeneous disease with a dismal prognosis for advanced tumors. Immune-associated cells in the microenvironment substantially impact LUAD formation and progression, which has gained increased attention in recent decades. Sphingolipids have a profound impact on tumor formation and immune infiltration. However, few researchers have focused on the utilization of sphingolipid variables in the prediction of LUAD prognosis. The goal of this work was to identify the major sphingolipid-related genes (SRGs) in LUAD and develop a valid prognostic model based on SRGs.MethodsThe most significant genes for sphingolipid metabolism (SM) were identified using the AUCell and WGCNA algorithms in conjunction with single-cell and bulk RNA-seq. LASSO and COX regression analysis was used to develop risk models, and patients were divided into high-and low-risk categories. External nine provided cohorts evaluated the correctness of the models. Differences in immune infiltration, mutation landscape, pathway enrichment, immune checkpoint expression, and immunotherapy were also further investigated in distinct subgroups. Finally, cell function assay was used to verify the role of CACYBP in LUAD cells.ResultsA total of 334 genes were selected as being most linked with SM activity for further investigation, and a risk model consisting of 11 genes was established using lasso and cox regression. According to the median risk value, patients were split into high- and low-risk groups, and the high-risk group had a worse prognosis. The low-risk group had more immune cell infiltration and higher expression of immune checkpoints, which illustrated that the low-risk group was more likely to benefit from immunotherapy. It was verified that CACYBP could increase the ability of LUAD cells to proliferate, invade, and migrate.ConclusionThe eleven-gene signature identified in this research may help physicians create individualized care plans for LUAD patients. CACYBP may be a new therapeutic target for patients with advanced LUAD. https://www.frontiersin.org/articles/10.3389/fimmu.2023.1115272/fulllung adenocarcinomasphingolipidCACYBPtumor immune microenvironmentimmunotherapy |
| spellingShingle | Pengpeng Zhang Shengbin Pei Zeitian Gong Yanlong Feng Xiao Zhang Fang Yang Wei Wang By integrating single-cell RNA-seq and bulk RNA-seq in sphingolipid metabolism, CACYBP was identified as a potential therapeutic target in lung adenocarcinoma Frontiers in Immunology lung adenocarcinoma sphingolipid CACYBP tumor immune microenvironment immunotherapy |
| title | By integrating single-cell RNA-seq and bulk RNA-seq in sphingolipid metabolism, CACYBP was identified as a potential therapeutic target in lung adenocarcinoma |
| title_full | By integrating single-cell RNA-seq and bulk RNA-seq in sphingolipid metabolism, CACYBP was identified as a potential therapeutic target in lung adenocarcinoma |
| title_fullStr | By integrating single-cell RNA-seq and bulk RNA-seq in sphingolipid metabolism, CACYBP was identified as a potential therapeutic target in lung adenocarcinoma |
| title_full_unstemmed | By integrating single-cell RNA-seq and bulk RNA-seq in sphingolipid metabolism, CACYBP was identified as a potential therapeutic target in lung adenocarcinoma |
| title_short | By integrating single-cell RNA-seq and bulk RNA-seq in sphingolipid metabolism, CACYBP was identified as a potential therapeutic target in lung adenocarcinoma |
| title_sort | by integrating single cell rna seq and bulk rna seq in sphingolipid metabolism cacybp was identified as a potential therapeutic target in lung adenocarcinoma |
| topic | lung adenocarcinoma sphingolipid CACYBP tumor immune microenvironment immunotherapy |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1115272/full |
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