Pancancer landscape analysis of the thymosin family identified TMSB10 as a potential prognostic biomarker and immunotherapy target in glioma
Abstract Background Thymosin family genes (TMSs), biologically important peptides with diverse intracellular and extracellular functions, have been shown to promote the progression of multiple cancers. However, multiomics characterization of TMSs and their role in human cancer prognosis has not been...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-09-01
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| Series: | Cancer Cell International |
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| Online Access: | https://doi.org/10.1186/s12935-022-02698-5 |
| _version_ | 1818024682788487168 |
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| author | Ye Xiong Yanhua Qi Ziwen Pan Shaobo Wang Boyan Li Bowen Feng Hao Xue Rongrong Zhao Gang Li |
| author_facet | Ye Xiong Yanhua Qi Ziwen Pan Shaobo Wang Boyan Li Bowen Feng Hao Xue Rongrong Zhao Gang Li |
| author_sort | Ye Xiong |
| collection | DOAJ |
| description | Abstract Background Thymosin family genes (TMSs), biologically important peptides with diverse intracellular and extracellular functions, have been shown to promote the progression of multiple cancers. However, multiomics characterization of TMSs and their role in human cancer prognosis has not been systematically performed. Methods We performed a comprehensive analysis of TMSs and thymosin β10 (TMSB10) using multiomics data from more than 10,000 tumor samples of 33 cancer types from The Cancer Genome Atlas (TCGA). We used single-sample gene set enrichment analysis (ssGSEA) and the gene set variation analysis (GSVA) algorithm to investigate the differences in tumor microenvironment (TME) cell infiltration and functional annotation for individual tumor samples, respectively. The role of TMSB10 in the malignant progression of glioma, the promotion of macrophage infiltration,and immunosuppressive polarization, and the combination drug efficacy were assessed via biological function assays. Results We comprehensively assessed genomic mutations, expression dysregulation, prognosis and immunotherapeutic response across 33 human cancer samples and showed that TMSB10 is specifically overexpressed in almost all types of cancer tissues. Further pan-cancer analysis showed that TMSB10 is closely related to the biological function, immune regulation and prognosis of glioma. Similar results were also found in several public glioma cohorts and our Qilu local cohort. Further integration with other biological experiments revealed the key roles of TMSB10 in the malignant progression of glioma, the promotion of macrophage infiltration and immunosuppressive polarization. We also identified multiple drugs targeting cells with high TMSB10 expression and validated that knockdown of TMSB10 improved the efficacy of selumetinib (a MEK1/2 inhibitor approved by the FDA for the treatment of neurofibromatosis-associated tumors) and anti-PD1 treatment in glioma. Conclusion These results indicate that TMSB10 holds promise as a novel prognostic marker and therapeutic target, providing a theoretical basis for the development of more effective and targeted clinical treatment strategies for glioma patients. |
| first_indexed | 2024-12-10T04:04:06Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1475-2867 |
| language | English |
| last_indexed | 2024-12-10T04:04:06Z |
| publishDate | 2022-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer Cell International |
| spelling | doaj.art-6dcf17d765a343fca2328ced8685bf212022-12-22T02:02:54ZengBMCCancer Cell International1475-28672022-09-0122112210.1186/s12935-022-02698-5Pancancer landscape analysis of the thymosin family identified TMSB10 as a potential prognostic biomarker and immunotherapy target in gliomaYe Xiong0Yanhua Qi1Ziwen Pan2Shaobo Wang3Boyan Li4Bowen Feng5Hao Xue6Rongrong Zhao7Gang Li8Department of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine, Institute of Brain and Brain-Inspired Science, Shandong UniversityDepartment of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine, Institute of Brain and Brain-Inspired Science, Shandong UniversityDepartment of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine, Institute of Brain and Brain-Inspired Science, Shandong UniversityDepartment of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine, Institute of Brain and Brain-Inspired Science, Shandong UniversityDepartment of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine, Institute of Brain and Brain-Inspired Science, Shandong UniversityDepartment of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine, Institute of Brain and Brain-Inspired Science, Shandong UniversityDepartment of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine, Institute of Brain and Brain-Inspired Science, Shandong UniversityDepartment of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine, Institute of Brain and Brain-Inspired Science, Shandong UniversityDepartment of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine, Institute of Brain and Brain-Inspired Science, Shandong UniversityAbstract Background Thymosin family genes (TMSs), biologically important peptides with diverse intracellular and extracellular functions, have been shown to promote the progression of multiple cancers. However, multiomics characterization of TMSs and their role in human cancer prognosis has not been systematically performed. Methods We performed a comprehensive analysis of TMSs and thymosin β10 (TMSB10) using multiomics data from more than 10,000 tumor samples of 33 cancer types from The Cancer Genome Atlas (TCGA). We used single-sample gene set enrichment analysis (ssGSEA) and the gene set variation analysis (GSVA) algorithm to investigate the differences in tumor microenvironment (TME) cell infiltration and functional annotation for individual tumor samples, respectively. The role of TMSB10 in the malignant progression of glioma, the promotion of macrophage infiltration,and immunosuppressive polarization, and the combination drug efficacy were assessed via biological function assays. Results We comprehensively assessed genomic mutations, expression dysregulation, prognosis and immunotherapeutic response across 33 human cancer samples and showed that TMSB10 is specifically overexpressed in almost all types of cancer tissues. Further pan-cancer analysis showed that TMSB10 is closely related to the biological function, immune regulation and prognosis of glioma. Similar results were also found in several public glioma cohorts and our Qilu local cohort. Further integration with other biological experiments revealed the key roles of TMSB10 in the malignant progression of glioma, the promotion of macrophage infiltration and immunosuppressive polarization. We also identified multiple drugs targeting cells with high TMSB10 expression and validated that knockdown of TMSB10 improved the efficacy of selumetinib (a MEK1/2 inhibitor approved by the FDA for the treatment of neurofibromatosis-associated tumors) and anti-PD1 treatment in glioma. Conclusion These results indicate that TMSB10 holds promise as a novel prognostic marker and therapeutic target, providing a theoretical basis for the development of more effective and targeted clinical treatment strategies for glioma patients.https://doi.org/10.1186/s12935-022-02698-5PancancerTMSB10GliomaTumor microenvironmentImmune checkpoint blockade |
| spellingShingle | Ye Xiong Yanhua Qi Ziwen Pan Shaobo Wang Boyan Li Bowen Feng Hao Xue Rongrong Zhao Gang Li Pancancer landscape analysis of the thymosin family identified TMSB10 as a potential prognostic biomarker and immunotherapy target in glioma Cancer Cell International Pancancer TMSB10 Glioma Tumor microenvironment Immune checkpoint blockade |
| title | Pancancer landscape analysis of the thymosin family identified TMSB10 as a potential prognostic biomarker and immunotherapy target in glioma |
| title_full | Pancancer landscape analysis of the thymosin family identified TMSB10 as a potential prognostic biomarker and immunotherapy target in glioma |
| title_fullStr | Pancancer landscape analysis of the thymosin family identified TMSB10 as a potential prognostic biomarker and immunotherapy target in glioma |
| title_full_unstemmed | Pancancer landscape analysis of the thymosin family identified TMSB10 as a potential prognostic biomarker and immunotherapy target in glioma |
| title_short | Pancancer landscape analysis of the thymosin family identified TMSB10 as a potential prognostic biomarker and immunotherapy target in glioma |
| title_sort | pancancer landscape analysis of the thymosin family identified tmsb10 as a potential prognostic biomarker and immunotherapy target in glioma |
| topic | Pancancer TMSB10 Glioma Tumor microenvironment Immune checkpoint blockade |
| url | https://doi.org/10.1186/s12935-022-02698-5 |
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