Progressions of the correlation between lipid metabolism and immune infiltration characteristics in gastric cancer and identification of BCHE as a potential biomarker
BackgroundGlobally, gastric cancer (GC) is a category of prevalent malignant tumors. Its high occurrence and fatality rates represent a severe threat to public health. According to recent research, lipid metabolism (LM) reprogramming impacts immune cells’ ordinary function and is critical for the on...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2024-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1327565/full |
| _version_ | 1797338402998190080 |
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| author | Shibo Wang Xiaojuan Huang Shufen Zhao Jing Lv Yi Li Shasha Wang Jing Guo Yan Wang Rui Wang Mengqi Zhang Wensheng Qiu |
| author_facet | Shibo Wang Xiaojuan Huang Shufen Zhao Jing Lv Yi Li Shasha Wang Jing Guo Yan Wang Rui Wang Mengqi Zhang Wensheng Qiu |
| author_sort | Shibo Wang |
| collection | DOAJ |
| description | BackgroundGlobally, gastric cancer (GC) is a category of prevalent malignant tumors. Its high occurrence and fatality rates represent a severe threat to public health. According to recent research, lipid metabolism (LM) reprogramming impacts immune cells’ ordinary function and is critical for the onset and development of cancer. Consequently, the article conducted a sophisticated bioinformatics analysis to explore the potential connection between LM and GC.MethodsWe first undertook a differential analysis of the TCGA queue to recognize lipid metabolism-related genes (LRGs) that are differentially expressed. Subsequently, we utilized the LASSO and Cox regression analyses to create a predictive signature and validated it with the GSE15459 cohort. Furthermore, we examined somatic mutations, immune checkpoints, tumor immune dysfunction and exclusion (TIDE), and drug sensitivity analyses to forecast the signature’s immunotherapy responses.ResultsKaplan-Meier (K-M) curves exhibited considerably longer OS and PFS (p<0.001) of the low-risk (LR) group. PCA analysis and ROC curves evaluated the model’s predictive efficacy. Additionally, GSEA analysis demonstrated that a multitude of carcinogenic and matrix-related pathways were much in the high-risk (HR) group. We then developed a nomogram to enhance its clinical practicality, and we quantitatively analyzed tumor-infiltrating immune cells (TIICs) using the CIBERSORT and ssGSEA algorithms. The low-risk group has a lower likelihood of immune escape and more effective in chemotherapy and immunotherapy. Eventually, we selected BCHE as a potential biomarker for further research and validated its expression. Next, we conducted a series of cell experiments (including CCK-8 assay, Colony formation assay, wound healing assay and Transwell assays) to prove the impact of BCHE on gastric cancer biological behavior.DiscussionOur research illustrated the possible consequences of lipid metabolism in GC, and we identified BCHE as a potential therapeutic target for GC. The LRG-based signature could independently forecast the outcome of GC patients and guide personalized therapy. |
| first_indexed | 2024-03-08T09:29:40Z |
| format | Article |
| id | doaj.art-264011482c8546aca2bc66ce8b8b4816 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-08T09:29:40Z |
| publishDate | 2024-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-264011482c8546aca2bc66ce8b8b48162024-01-31T04:37:57ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-01-011510.3389/fimmu.2024.13275651327565Progressions of the correlation between lipid metabolism and immune infiltration characteristics in gastric cancer and identification of BCHE as a potential biomarkerShibo Wang0Xiaojuan Huang1Shufen Zhao2Jing Lv3Yi Li4Shasha Wang5Jing Guo6Yan Wang7Rui Wang8Mengqi Zhang9Wensheng Qiu10Department of Oncology, The Affiliated Hospital of Qingdao University, Qingdao, ChinaDepartment of Oncology, The Affiliated Hospital of Qingdao University, Qingdao, ChinaDepartment of Oncology, The Affiliated Hospital of Qingdao University, Qingdao, ChinaDepartment of Oncology, The Affiliated Hospital of Qingdao University, Qingdao, ChinaDepartment of Dermatology, The Affiliated Hospital of Qingdao University, Qingdao, ChinaDepartment of Oncology, The Affiliated Hospital of Qingdao University, Qingdao, ChinaDepartment of Oncology, The Affiliated Hospital of Qingdao University, Qingdao, ChinaDepartment of Oncology, The Affiliated Hospital of Qingdao University, Qingdao, ChinaDepartment of Oncology, The Affiliated Hospital of Qingdao University, Qingdao, ChinaDepartment of Oncology, The Affiliated Hospital of Qingdao University, Qingdao, ChinaDepartment of Oncology, The Affiliated Hospital of Qingdao University, Qingdao, ChinaBackgroundGlobally, gastric cancer (GC) is a category of prevalent malignant tumors. Its high occurrence and fatality rates represent a severe threat to public health. According to recent research, lipid metabolism (LM) reprogramming impacts immune cells’ ordinary function and is critical for the onset and development of cancer. Consequently, the article conducted a sophisticated bioinformatics analysis to explore the potential connection between LM and GC.MethodsWe first undertook a differential analysis of the TCGA queue to recognize lipid metabolism-related genes (LRGs) that are differentially expressed. Subsequently, we utilized the LASSO and Cox regression analyses to create a predictive signature and validated it with the GSE15459 cohort. Furthermore, we examined somatic mutations, immune checkpoints, tumor immune dysfunction and exclusion (TIDE), and drug sensitivity analyses to forecast the signature’s immunotherapy responses.ResultsKaplan-Meier (K-M) curves exhibited considerably longer OS and PFS (p<0.001) of the low-risk (LR) group. PCA analysis and ROC curves evaluated the model’s predictive efficacy. Additionally, GSEA analysis demonstrated that a multitude of carcinogenic and matrix-related pathways were much in the high-risk (HR) group. We then developed a nomogram to enhance its clinical practicality, and we quantitatively analyzed tumor-infiltrating immune cells (TIICs) using the CIBERSORT and ssGSEA algorithms. The low-risk group has a lower likelihood of immune escape and more effective in chemotherapy and immunotherapy. Eventually, we selected BCHE as a potential biomarker for further research and validated its expression. Next, we conducted a series of cell experiments (including CCK-8 assay, Colony formation assay, wound healing assay and Transwell assays) to prove the impact of BCHE on gastric cancer biological behavior.DiscussionOur research illustrated the possible consequences of lipid metabolism in GC, and we identified BCHE as a potential therapeutic target for GC. The LRG-based signature could independently forecast the outcome of GC patients and guide personalized therapy.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1327565/fullgastric cancerlipid metabolismprognostic signatureTIICsBChEimmunotherapy |
| spellingShingle | Shibo Wang Xiaojuan Huang Shufen Zhao Jing Lv Yi Li Shasha Wang Jing Guo Yan Wang Rui Wang Mengqi Zhang Wensheng Qiu Progressions of the correlation between lipid metabolism and immune infiltration characteristics in gastric cancer and identification of BCHE as a potential biomarker Frontiers in Immunology gastric cancer lipid metabolism prognostic signature TIICs BChE immunotherapy |
| title | Progressions of the correlation between lipid metabolism and immune infiltration characteristics in gastric cancer and identification of BCHE as a potential biomarker |
| title_full | Progressions of the correlation between lipid metabolism and immune infiltration characteristics in gastric cancer and identification of BCHE as a potential biomarker |
| title_fullStr | Progressions of the correlation between lipid metabolism and immune infiltration characteristics in gastric cancer and identification of BCHE as a potential biomarker |
| title_full_unstemmed | Progressions of the correlation between lipid metabolism and immune infiltration characteristics in gastric cancer and identification of BCHE as a potential biomarker |
| title_short | Progressions of the correlation between lipid metabolism and immune infiltration characteristics in gastric cancer and identification of BCHE as a potential biomarker |
| title_sort | progressions of the correlation between lipid metabolism and immune infiltration characteristics in gastric cancer and identification of bche as a potential biomarker |
| topic | gastric cancer lipid metabolism prognostic signature TIICs BChE immunotherapy |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1327565/full |
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