A prognostic signature of Glutathione metabolism-associated long non-coding RNAs for lung adenocarcinoma with immune microenvironment insights
BackgroundGlutathione (GSH) metabolism supports tumor redox balance and drug resistance, while long non-coding RNAs (lncRNAs) influence lung adenocarcinoma (LUAD) progression. This study developed a prognostic model using GSH-related lncRNAs to predict LUAD outcomes and assess tumor immunity.Methods...
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Frontiers Media S.A.
2025-02-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1477437/full |
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| author | Junxi Hu Junxi Hu Shuyu Tian Shuyu Tian Qingwen Liu Qingwen Liu Jiaqi Hou Jiaqi Hou Jun wu Jun wu Xiaolin Wang Xiaolin Wang Yusheng Shu Yusheng Shu |
| author_facet | Junxi Hu Junxi Hu Shuyu Tian Shuyu Tian Qingwen Liu Qingwen Liu Jiaqi Hou Jiaqi Hou Jun wu Jun wu Xiaolin Wang Xiaolin Wang Yusheng Shu Yusheng Shu |
| author_sort | Junxi Hu |
| collection | DOAJ |
| description | BackgroundGlutathione (GSH) metabolism supports tumor redox balance and drug resistance, while long non-coding RNAs (lncRNAs) influence lung adenocarcinoma (LUAD) progression. This study developed a prognostic model using GSH-related lncRNAs to predict LUAD outcomes and assess tumor immunity.MethodsThis study analyzed survival data from The Cancer Genome Atlas (TCGA) and identified GSH metabolism-related lncRNAs using Pearson correlation. A prognostic model was built with Cox and Least Absolute Shrinkage and Selection Operator (LASSO) methods and validated by Kaplan-Meier analysis, Receiver Operating Characteristic (ROC) curves, and Principal Component Analysis (PCA). Functional analysis revealed immune infiltration and drug sensitivity differences. Quantitative PCR and experimental studies confirmed the role of lnc-AL162632.3 in LUAD.ResultsOur model included a total of nine lncRNAs, namely AL162632.3, AL360270.1, LINC00707, DEPDC1-AS1, GSEC, LINC01711, AL078590.2, AC026355.2, and AL096701.4. The model effectively forecasted patient survival, and the nomogram, incorporating additional clinical risk factors, satisfied clinical needs adequately. Patient stratification based on model scores revealed significant disparities in immune cell composition, functionality, and mutations between groups. Additionally, variations were noted in the IC50 values for key lung cancer medications such as Cisplatin, Docetaxel, and Paclitaxel. In vitro cell experiment results showed that AL162632.3 was markedly upregulated, while AC026355.2 tended to be downregulated across these cell lines. Ultimately, suppressing lnc-AL162632.3 markedly reduced the growth, mobility, and invasiveness of lung cancer cells.ConclusionThis study identified GSH metabolism-related lncRNAs as key prognostic factors in LUAD and developed a model for risk stratification. High-risk patients showed increased tumor mutation burden (TMB) and stemness, emphasizing the potential of personalized immunotherapy to improve survival outcomes. |
| format | Article |
| id | doaj-art-3aa7c5f9ec3e44d6816b31cbc8eb4f43 |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj-art-3aa7c5f9ec3e44d6816b31cbc8eb4f432025-02-10T06:48:43ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-02-011610.3389/fimmu.2025.14774371477437A prognostic signature of Glutathione metabolism-associated long non-coding RNAs for lung adenocarcinoma with immune microenvironment insightsJunxi Hu0Junxi Hu1Shuyu Tian2Shuyu Tian3Qingwen Liu4Qingwen Liu5Jiaqi Hou6Jiaqi Hou7Jun wu8Jun wu9Xiaolin Wang10Xiaolin Wang11Yusheng Shu12Yusheng Shu13Clinical Medical College, Yangzhou University, Yangzhou, ChinaDepartment of Thoracic Surgery, Northern Jiangsu People’s Hospital, Yangzhou, ChinaDepartment of Thoracic Surgery, Northern Jiangsu People’s Hospital, Yangzhou, ChinaDalian Medical University, Dalian, ChinaDepartment of Thoracic Surgery, Northern Jiangsu People’s Hospital, Yangzhou, ChinaDalian Medical University, Dalian, ChinaDepartment of Thoracic Surgery, Northern Jiangsu People’s Hospital, Yangzhou, ChinaDalian Medical University, Dalian, ChinaClinical Medical College, Yangzhou University, Yangzhou, ChinaDepartment of Thoracic Surgery, Northern Jiangsu People’s Hospital, Yangzhou, ChinaClinical Medical College, Yangzhou University, Yangzhou, ChinaDepartment of Thoracic Surgery, Northern Jiangsu People’s Hospital, Yangzhou, ChinaClinical Medical College, Yangzhou University, Yangzhou, ChinaDepartment of Thoracic Surgery, Northern Jiangsu People’s Hospital, Yangzhou, ChinaBackgroundGlutathione (GSH) metabolism supports tumor redox balance and drug resistance, while long non-coding RNAs (lncRNAs) influence lung adenocarcinoma (LUAD) progression. This study developed a prognostic model using GSH-related lncRNAs to predict LUAD outcomes and assess tumor immunity.MethodsThis study analyzed survival data from The Cancer Genome Atlas (TCGA) and identified GSH metabolism-related lncRNAs using Pearson correlation. A prognostic model was built with Cox and Least Absolute Shrinkage and Selection Operator (LASSO) methods and validated by Kaplan-Meier analysis, Receiver Operating Characteristic (ROC) curves, and Principal Component Analysis (PCA). Functional analysis revealed immune infiltration and drug sensitivity differences. Quantitative PCR and experimental studies confirmed the role of lnc-AL162632.3 in LUAD.ResultsOur model included a total of nine lncRNAs, namely AL162632.3, AL360270.1, LINC00707, DEPDC1-AS1, GSEC, LINC01711, AL078590.2, AC026355.2, and AL096701.4. The model effectively forecasted patient survival, and the nomogram, incorporating additional clinical risk factors, satisfied clinical needs adequately. Patient stratification based on model scores revealed significant disparities in immune cell composition, functionality, and mutations between groups. Additionally, variations were noted in the IC50 values for key lung cancer medications such as Cisplatin, Docetaxel, and Paclitaxel. In vitro cell experiment results showed that AL162632.3 was markedly upregulated, while AC026355.2 tended to be downregulated across these cell lines. Ultimately, suppressing lnc-AL162632.3 markedly reduced the growth, mobility, and invasiveness of lung cancer cells.ConclusionThis study identified GSH metabolism-related lncRNAs as key prognostic factors in LUAD and developed a model for risk stratification. High-risk patients showed increased tumor mutation burden (TMB) and stemness, emphasizing the potential of personalized immunotherapy to improve survival outcomes.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1477437/fulllung adenocarcinomaGlutathione metabolismlncRNAprognostic predictionimmune microenvironment |
| spellingShingle | Junxi Hu Junxi Hu Shuyu Tian Shuyu Tian Qingwen Liu Qingwen Liu Jiaqi Hou Jiaqi Hou Jun wu Jun wu Xiaolin Wang Xiaolin Wang Yusheng Shu Yusheng Shu A prognostic signature of Glutathione metabolism-associated long non-coding RNAs for lung adenocarcinoma with immune microenvironment insights Frontiers in Immunology lung adenocarcinoma Glutathione metabolism lncRNA prognostic prediction immune microenvironment |
| title | A prognostic signature of Glutathione metabolism-associated long non-coding RNAs for lung adenocarcinoma with immune microenvironment insights |
| title_full | A prognostic signature of Glutathione metabolism-associated long non-coding RNAs for lung adenocarcinoma with immune microenvironment insights |
| title_fullStr | A prognostic signature of Glutathione metabolism-associated long non-coding RNAs for lung adenocarcinoma with immune microenvironment insights |
| title_full_unstemmed | A prognostic signature of Glutathione metabolism-associated long non-coding RNAs for lung adenocarcinoma with immune microenvironment insights |
| title_short | A prognostic signature of Glutathione metabolism-associated long non-coding RNAs for lung adenocarcinoma with immune microenvironment insights |
| title_sort | prognostic signature of glutathione metabolism associated long non coding rnas for lung adenocarcinoma with immune microenvironment insights |
| topic | lung adenocarcinoma Glutathione metabolism lncRNA prognostic prediction immune microenvironment |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1477437/full |
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