Prognostic signature of lipid metabolism associated LncRNAs predict prognosis and treatment of lung adenocarcinoma
BackgroundLung adenocarcinoma (LUAD) is the most predominant histological subtype of lung cancer. Abnormal lipid metabolism is closely related to the development of LUAD. LncRNAs are involved in the regulation of various lipid metabolism-related genes in various cancer cells including LUAD. Here, we...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-11-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.986367/full |
| _version_ | 1811256308796489728 |
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| author | Jie Zhao Guangjian Li Guangqiang Zhao Wei Wang Zhenghai Shen Yantao Yang Yunchao Huang Lianhua Ye |
| author_facet | Jie Zhao Guangjian Li Guangqiang Zhao Wei Wang Zhenghai Shen Yantao Yang Yunchao Huang Lianhua Ye |
| author_sort | Jie Zhao |
| collection | DOAJ |
| description | BackgroundLung adenocarcinoma (LUAD) is the most predominant histological subtype of lung cancer. Abnormal lipid metabolism is closely related to the development of LUAD. LncRNAs are involved in the regulation of various lipid metabolism-related genes in various cancer cells including LUAD. Here, we aimed to identify lipid metabolism-related lncRNAs associated with LUAD prognosis and to propose a new prognostic signature.MethodsFirst, differentially expressed lncRNAs (DE-lncRNAs) from the TCGA-LUAD and the GSE31210 dataset were identified. Then the correlation analysis between DE-lncRNAs and lipid metabolism genes was performed to screen lipid metabolism-related lncRNAs. Cox regression analyses were performed in the training set to establish a prognostic model and the model was validated in the testing set and the validation set. Moreover, The role of this model in the underlying molecular mechanisms, immunotherapy, and chemotherapeutic drug sensitivity analysis was predicted by methods such as Gene Set Enrichment Analysis, immune infiltration, tumor mutational burden (TMB), neoantigen, Tumor Immune Dysfunction and Exclusion, chemosensitivity analysis between the high- and low-risk groups. The diagnostic ability of prognostic lncRNAs has also been validated. Finally, we validated the expression levels of selected prognostic lncRNAs by quantitative real-time polymerase chain reaction (qRT-PCR).ResultsThe prognostic model was constructed based on four prognostic lncRNAs (LINC00857, EP300-AS1, TBX5-AS1, SNHG3) related to lipid metabolism. The receiver operating characteristic curve (ROC) and Kaplan Meier (KM) curves of the risk model showed their validity. The results of Gene Set Enrichment Analysis suggested that differentially expressed genes in high- and low-risk groups were mainly enriched in immune response and cell cycle. There statistical differences in TMB and neoantigen between high- and low-risk groups. Drug sensitivity analysis suggested that patients with low risk scores may have better chemotherapy outcomes. The results of qRT-PCR were suggesting that compared with the normal group, the expressions of EP300-AS1 and TBX5-AS1 were down-regulated in the tumor group, while the expressions of LINC00857 and SNHG3 were up-regulated. The four prognostic lncRNAs had good diagnostic capabilities, and the overall diagnostic model of the four prognostic lncRNAs was more effective.ConclusionA total of 4 prognostic lncRNAs related to lipid metabolism were obtained and an effective risk model was constructed. |
| first_indexed | 2024-04-12T17:38:11Z |
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| id | doaj.art-f6f4c3e3e64d451bbe41f14412fdfda9 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-12T17:38:11Z |
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| series | Frontiers in Oncology |
| spelling | doaj.art-f6f4c3e3e64d451bbe41f14412fdfda92022-12-22T03:22:54ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-11-011210.3389/fonc.2022.986367986367Prognostic signature of lipid metabolism associated LncRNAs predict prognosis and treatment of lung adenocarcinomaJie Zhao0Guangjian Li1Guangqiang Zhao2Wei Wang3Zhenghai Shen4Yantao Yang5Yunchao Huang6Lianhua Ye7Department of Thoracic Surgery, The Third Affiliated Hospital of Kunming Medical University (Yunnan Cancer Hospital), Kunming, ChinaDepartment of Thoracic Surgery, The Third Affiliated Hospital of Kunming Medical University (Yunnan Cancer Hospital), Kunming, ChinaDepartment of Thoracic Surgery, The Third Affiliated Hospital of Kunming Medical University (Yunnan Cancer Hospital), Kunming, ChinaDepartment of Thoracic Surgery, Taihe Hospital (Hubei University of Medicine), Shiyan, ChinaDepartment of Thoracic Surgery, The Third Affiliated Hospital of Kunming Medical University (Yunnan Cancer Hospital), Kunming, ChinaDepartment of Thoracic Surgery, The Third Affiliated Hospital of Kunming Medical University (Yunnan Cancer Hospital), Kunming, ChinaDepartment of Thoracic Surgery, The Third Affiliated Hospital of Kunming Medical University (Yunnan Cancer Hospital), Kunming, ChinaDepartment of Thoracic Surgery, The Third Affiliated Hospital of Kunming Medical University (Yunnan Cancer Hospital), Kunming, ChinaBackgroundLung adenocarcinoma (LUAD) is the most predominant histological subtype of lung cancer. Abnormal lipid metabolism is closely related to the development of LUAD. LncRNAs are involved in the regulation of various lipid metabolism-related genes in various cancer cells including LUAD. Here, we aimed to identify lipid metabolism-related lncRNAs associated with LUAD prognosis and to propose a new prognostic signature.MethodsFirst, differentially expressed lncRNAs (DE-lncRNAs) from the TCGA-LUAD and the GSE31210 dataset were identified. Then the correlation analysis between DE-lncRNAs and lipid metabolism genes was performed to screen lipid metabolism-related lncRNAs. Cox regression analyses were performed in the training set to establish a prognostic model and the model was validated in the testing set and the validation set. Moreover, The role of this model in the underlying molecular mechanisms, immunotherapy, and chemotherapeutic drug sensitivity analysis was predicted by methods such as Gene Set Enrichment Analysis, immune infiltration, tumor mutational burden (TMB), neoantigen, Tumor Immune Dysfunction and Exclusion, chemosensitivity analysis between the high- and low-risk groups. The diagnostic ability of prognostic lncRNAs has also been validated. Finally, we validated the expression levels of selected prognostic lncRNAs by quantitative real-time polymerase chain reaction (qRT-PCR).ResultsThe prognostic model was constructed based on four prognostic lncRNAs (LINC00857, EP300-AS1, TBX5-AS1, SNHG3) related to lipid metabolism. The receiver operating characteristic curve (ROC) and Kaplan Meier (KM) curves of the risk model showed their validity. The results of Gene Set Enrichment Analysis suggested that differentially expressed genes in high- and low-risk groups were mainly enriched in immune response and cell cycle. There statistical differences in TMB and neoantigen between high- and low-risk groups. Drug sensitivity analysis suggested that patients with low risk scores may have better chemotherapy outcomes. The results of qRT-PCR were suggesting that compared with the normal group, the expressions of EP300-AS1 and TBX5-AS1 were down-regulated in the tumor group, while the expressions of LINC00857 and SNHG3 were up-regulated. The four prognostic lncRNAs had good diagnostic capabilities, and the overall diagnostic model of the four prognostic lncRNAs was more effective.ConclusionA total of 4 prognostic lncRNAs related to lipid metabolism were obtained and an effective risk model was constructed.https://www.frontiersin.org/articles/10.3389/fonc.2022.986367/fulllung adenocarcinomalncRNAprognosticlipid metabolism genessignature |
| spellingShingle | Jie Zhao Guangjian Li Guangqiang Zhao Wei Wang Zhenghai Shen Yantao Yang Yunchao Huang Lianhua Ye Prognostic signature of lipid metabolism associated LncRNAs predict prognosis and treatment of lung adenocarcinoma Frontiers in Oncology lung adenocarcinoma lncRNA prognostic lipid metabolism genes signature |
| title | Prognostic signature of lipid metabolism associated LncRNAs predict prognosis and treatment of lung adenocarcinoma |
| title_full | Prognostic signature of lipid metabolism associated LncRNAs predict prognosis and treatment of lung adenocarcinoma |
| title_fullStr | Prognostic signature of lipid metabolism associated LncRNAs predict prognosis and treatment of lung adenocarcinoma |
| title_full_unstemmed | Prognostic signature of lipid metabolism associated LncRNAs predict prognosis and treatment of lung adenocarcinoma |
| title_short | Prognostic signature of lipid metabolism associated LncRNAs predict prognosis and treatment of lung adenocarcinoma |
| title_sort | prognostic signature of lipid metabolism associated lncrnas predict prognosis and treatment of lung adenocarcinoma |
| topic | lung adenocarcinoma lncRNA prognostic lipid metabolism genes signature |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.986367/full |
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