Development of a Hallmark Pathway-Related Gene Signature Associated with Immune Response for Lower Grade Gliomas
Although some biomarkers have been used to predict prognosis of lower-grade gliomas (LGGs), a pathway-related signature associated with immune response has not been developed. A key signaling pathway was determined according to the lowest adjusted p value among 50 hallmark pathways. The least absolu...
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| Format: | Article |
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MDPI AG
2022-10-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/19/11971 |
| _version_ | 1797478783038521344 |
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| author | Guichuan Lai Xiaoni Zhong Hui Liu Jielian Deng Kangjie Li Biao Xie |
| author_facet | Guichuan Lai Xiaoni Zhong Hui Liu Jielian Deng Kangjie Li Biao Xie |
| author_sort | Guichuan Lai |
| collection | DOAJ |
| description | Although some biomarkers have been used to predict prognosis of lower-grade gliomas (LGGs), a pathway-related signature associated with immune response has not been developed. A key signaling pathway was determined according to the lowest adjusted p value among 50 hallmark pathways. The least absolute shrinkage and selection operator (LASSO) and stepwise multivariate Cox analyses were performed to construct a pathway-related gene signature. Somatic mutation, drug sensitivity and prediction of immunotherapy analyses were conducted to reveal the value of this signature in targeted therapies. In this study, an allograft rejection (AR) pathway was considered as a crucial signaling pathway, and we constructed an AR-related five-gene signature, which can independently predict the prognosis of LGGs. High-AR LGG patients had higher tumor mutation burden (TMB), Immunophenscore (IPS), IMmuno-PREdictive Score (IMPRES), T cell-inflamed gene expression profile (GEP) score and MHC I association immunoscore (MIAS) than low-AR patients. Most importantly, our signature can be validated in four immunotherapy cohorts. Furthermore, IC50 values of the six classic chemotherapeutic drugs were significantly elevated in the low-AR group compared with the high-AR group. This signature might be regarded as an underlying biomarker in predicting prognosis for LGGs, possibly providing more therapeutic strategies for future clinical research. |
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| format | Article |
| id | doaj.art-a46688a9fe7a43e7995dc545c65ff3ff |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T21:36:32Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-a46688a9fe7a43e7995dc545c65ff3ff2023-11-23T20:42:22ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-10-0123191197110.3390/ijms231911971Development of a Hallmark Pathway-Related Gene Signature Associated with Immune Response for Lower Grade GliomasGuichuan Lai0Xiaoni Zhong1Hui Liu2Jielian Deng3Kangjie Li4Biao Xie5Department of Epidemiology and Health Statistics, School of Public Health, Chongqing Medical University, Yixue Road, Chongqing 400016, ChinaDepartment of Epidemiology and Health Statistics, School of Public Health, Chongqing Medical University, Yixue Road, Chongqing 400016, ChinaDepartment of Epidemiology and Health Statistics, School of Public Health, Chongqing Medical University, Yixue Road, Chongqing 400016, ChinaDepartment of Epidemiology and Health Statistics, School of Public Health, Chongqing Medical University, Yixue Road, Chongqing 400016, ChinaDepartment of Epidemiology and Health Statistics, School of Public Health, Chongqing Medical University, Yixue Road, Chongqing 400016, ChinaDepartment of Epidemiology and Health Statistics, School of Public Health, Chongqing Medical University, Yixue Road, Chongqing 400016, ChinaAlthough some biomarkers have been used to predict prognosis of lower-grade gliomas (LGGs), a pathway-related signature associated with immune response has not been developed. A key signaling pathway was determined according to the lowest adjusted p value among 50 hallmark pathways. The least absolute shrinkage and selection operator (LASSO) and stepwise multivariate Cox analyses were performed to construct a pathway-related gene signature. Somatic mutation, drug sensitivity and prediction of immunotherapy analyses were conducted to reveal the value of this signature in targeted therapies. In this study, an allograft rejection (AR) pathway was considered as a crucial signaling pathway, and we constructed an AR-related five-gene signature, which can independently predict the prognosis of LGGs. High-AR LGG patients had higher tumor mutation burden (TMB), Immunophenscore (IPS), IMmuno-PREdictive Score (IMPRES), T cell-inflamed gene expression profile (GEP) score and MHC I association immunoscore (MIAS) than low-AR patients. Most importantly, our signature can be validated in four immunotherapy cohorts. Furthermore, IC50 values of the six classic chemotherapeutic drugs were significantly elevated in the low-AR group compared with the high-AR group. This signature might be regarded as an underlying biomarker in predicting prognosis for LGGs, possibly providing more therapeutic strategies for future clinical research.https://www.mdpi.com/1422-0067/23/19/11971lower grade gliomassignaling pathwaysimmune responseallograft rejectionbiomarkersprognosis |
| spellingShingle | Guichuan Lai Xiaoni Zhong Hui Liu Jielian Deng Kangjie Li Biao Xie Development of a Hallmark Pathway-Related Gene Signature Associated with Immune Response for Lower Grade Gliomas International Journal of Molecular Sciences lower grade gliomas signaling pathways immune response allograft rejection biomarkers prognosis |
| title | Development of a Hallmark Pathway-Related Gene Signature Associated with Immune Response for Lower Grade Gliomas |
| title_full | Development of a Hallmark Pathway-Related Gene Signature Associated with Immune Response for Lower Grade Gliomas |
| title_fullStr | Development of a Hallmark Pathway-Related Gene Signature Associated with Immune Response for Lower Grade Gliomas |
| title_full_unstemmed | Development of a Hallmark Pathway-Related Gene Signature Associated with Immune Response for Lower Grade Gliomas |
| title_short | Development of a Hallmark Pathway-Related Gene Signature Associated with Immune Response for Lower Grade Gliomas |
| title_sort | development of a hallmark pathway related gene signature associated with immune response for lower grade gliomas |
| topic | lower grade gliomas signaling pathways immune response allograft rejection biomarkers prognosis |
| url | https://www.mdpi.com/1422-0067/23/19/11971 |
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