A novel ubiquitin-related genes-based signature demonstrated values in prognostic prediction, immune landscape sculpture and therapeutic options in laryngeal cancer
BackgroundLaryngeal cancer (LC) is characterized by high mortality and remains challenging in prognostic evaluation and treatment benefits. Ubiquitin-related genes (UbRGs) are widely involved in cancer initiation and progression, but their potential value in LC is unknown.MethodsRNA-seq and clinical...
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Frontiers Media S.A.
2025-03-01
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2025.1513948/full |
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| author | Lu Liu Lu Liu Lu Liu Lu Liu Bing Wang Xiaoya Ma Xiaoya Ma Lei Tan Lei Tan Lei Tan Xudong Wei Xudong Wei |
| author_facet | Lu Liu Lu Liu Lu Liu Lu Liu Bing Wang Xiaoya Ma Xiaoya Ma Lei Tan Lei Tan Lei Tan Xudong Wei Xudong Wei |
| author_sort | Lu Liu |
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| description | BackgroundLaryngeal cancer (LC) is characterized by high mortality and remains challenging in prognostic evaluation and treatment benefits. Ubiquitin-related genes (UbRGs) are widely involved in cancer initiation and progression, but their potential value in LC is unknown.MethodsRNA-seq and clinical data of LC were obtained from TCGA and GEO. UbRGs that independently influenced the overall survival (OS) of LC patients were screened with differential expression, COX and LASSO regression analyses. A prognostic signature was then established and assessed for its predictive value, stability and applicability using Kaplan-Meier analysis and receiver operating characteristic curves. The nomogram was further generated in combination with the signature and clinical characteristics. Characterization of immune properties and prediction of drug sensitivity were investigated on the signature-based subgroups using a panel of in silico platforms. Verification of gene expression was conducted with Western blot, qRT-PCR and ELISA, ultimately.ResultsPPARG, LCK and LHX1 were identified and employed to construct the UbRGs-based prognostic signature, showing a strong ability to discriminate LC patients with distinct OS in TCGA-LC and GSE65858, and excellent applicability in most clinical conditions. The nomogram showed higher predictive value and net clinical benefit than traditional indicators. As evaluated, the low-risk group had a more activated immune function, higher infiltration of anti-cancer immune cells and stronger expression of immune-promoting cytokines than the high-risk group. Immune properties were also correlated with individual signature genes. PPARG and LHX1 were negatively correlated, whereas LCK positively correlated, with the immuno-promoting microenvironment. Additionally, chemotherapy would be more effective in high-risk patients, while immune checkpoint inhibitors would be more effective in low-risk patients. Finally, dysregulation of the signature genes was confirmed in LC cell lines by Western blot, and PPARG knockdown significantly reduced the expression of the immunosuppressive cytokines IL6, TGFB1, TGFB2 and VEGFC by qRT-PCR and ELISA.ConclusionWe have developed a UbRGs-based signature for LC prognostic evaluation that is valuable in clinical application, indicative of the immune microenvironment and beneficial for individualized treatment guidance. |
| format | Article |
| id | doaj-art-cab09d1e682b4f00a8bcc12c75cf4fda |
| institution | Kabale University |
| issn | 1663-9812 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Pharmacology |
| spelling | doaj-art-cab09d1e682b4f00a8bcc12c75cf4fda2025-08-20T03:42:53ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-03-011610.3389/fphar.2025.15139481513948A novel ubiquitin-related genes-based signature demonstrated values in prognostic prediction, immune landscape sculpture and therapeutic options in laryngeal cancerLu Liu0Lu Liu1Lu Liu2Lu Liu3Bing Wang4Xiaoya Ma5Xiaoya Ma6Lei Tan7Lei Tan8Lei Tan9Xudong Wei10Xudong Wei11The First Clinical Medical College of Lanzhou University, Lanzhou, ChinaDepartment of E.N.T., Gansu Provincial Hospital, Lanzhou, ChinaCenter for Energy Metabolism and Reproduction, Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, ChinaInnovation Center of Suzhou Nanjing Medical University, Suzhou, ChinaPediatric Heart Disease Treatment Center, Jiangxi Provincial Children’s Hospital, Nanchang, ChinaCenter for Energy Metabolism and Reproduction, Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, ChinaDepartment of Cardiology, Shenzhen Guangming District People’s Hospital, Shenzhen, ChinaInnovation Center of Suzhou Nanjing Medical University, Suzhou, ChinaState Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, Nanjing, ChinaNational Center of Technology Innovation for Biopharmaceuticals, Suzhou, ChinaThe First Clinical Medical College of Lanzhou University, Lanzhou, ChinaDepartment of E.N.T., Gansu Provincial Hospital, Lanzhou, ChinaBackgroundLaryngeal cancer (LC) is characterized by high mortality and remains challenging in prognostic evaluation and treatment benefits. Ubiquitin-related genes (UbRGs) are widely involved in cancer initiation and progression, but their potential value in LC is unknown.MethodsRNA-seq and clinical data of LC were obtained from TCGA and GEO. UbRGs that independently influenced the overall survival (OS) of LC patients were screened with differential expression, COX and LASSO regression analyses. A prognostic signature was then established and assessed for its predictive value, stability and applicability using Kaplan-Meier analysis and receiver operating characteristic curves. The nomogram was further generated in combination with the signature and clinical characteristics. Characterization of immune properties and prediction of drug sensitivity were investigated on the signature-based subgroups using a panel of in silico platforms. Verification of gene expression was conducted with Western blot, qRT-PCR and ELISA, ultimately.ResultsPPARG, LCK and LHX1 were identified and employed to construct the UbRGs-based prognostic signature, showing a strong ability to discriminate LC patients with distinct OS in TCGA-LC and GSE65858, and excellent applicability in most clinical conditions. The nomogram showed higher predictive value and net clinical benefit than traditional indicators. As evaluated, the low-risk group had a more activated immune function, higher infiltration of anti-cancer immune cells and stronger expression of immune-promoting cytokines than the high-risk group. Immune properties were also correlated with individual signature genes. PPARG and LHX1 were negatively correlated, whereas LCK positively correlated, with the immuno-promoting microenvironment. Additionally, chemotherapy would be more effective in high-risk patients, while immune checkpoint inhibitors would be more effective in low-risk patients. Finally, dysregulation of the signature genes was confirmed in LC cell lines by Western blot, and PPARG knockdown significantly reduced the expression of the immunosuppressive cytokines IL6, TGFB1, TGFB2 and VEGFC by qRT-PCR and ELISA.ConclusionWe have developed a UbRGs-based signature for LC prognostic evaluation that is valuable in clinical application, indicative of the immune microenvironment and beneficial for individualized treatment guidance.https://www.frontiersin.org/articles/10.3389/fphar.2025.1513948/fulllaryngeal cancerubiquitin-related genes-based signatureprognosis predictionimmune landscape sculpturetherapeutic options |
| spellingShingle | Lu Liu Lu Liu Lu Liu Lu Liu Bing Wang Xiaoya Ma Xiaoya Ma Lei Tan Lei Tan Lei Tan Xudong Wei Xudong Wei A novel ubiquitin-related genes-based signature demonstrated values in prognostic prediction, immune landscape sculpture and therapeutic options in laryngeal cancer Frontiers in Pharmacology laryngeal cancer ubiquitin-related genes-based signature prognosis prediction immune landscape sculpture therapeutic options |
| title | A novel ubiquitin-related genes-based signature demonstrated values in prognostic prediction, immune landscape sculpture and therapeutic options in laryngeal cancer |
| title_full | A novel ubiquitin-related genes-based signature demonstrated values in prognostic prediction, immune landscape sculpture and therapeutic options in laryngeal cancer |
| title_fullStr | A novel ubiquitin-related genes-based signature demonstrated values in prognostic prediction, immune landscape sculpture and therapeutic options in laryngeal cancer |
| title_full_unstemmed | A novel ubiquitin-related genes-based signature demonstrated values in prognostic prediction, immune landscape sculpture and therapeutic options in laryngeal cancer |
| title_short | A novel ubiquitin-related genes-based signature demonstrated values in prognostic prediction, immune landscape sculpture and therapeutic options in laryngeal cancer |
| title_sort | novel ubiquitin related genes based signature demonstrated values in prognostic prediction immune landscape sculpture and therapeutic options in laryngeal cancer |
| topic | laryngeal cancer ubiquitin-related genes-based signature prognosis prediction immune landscape sculpture therapeutic options |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2025.1513948/full |
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