Construction of immunotherapy-related prognostic gene signature and small molecule drug prediction for cutaneous melanoma
BackgroundCutaneous melanoma (CM), a kind of skin cancer with a high rate of advanced mortality, exhibits a wide variety of driver and transmitter gene alterations in the immunological tumor microenvironment (TME) associated with tumor cell survival and proliferation.MethodsWe analyzed the immunolog...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-07-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.939385/full |
| _version_ | 1818477484093472768 |
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| author | Jiahua Xing Jiahua Xing Ziqi Jia Yan Li Yan Han |
| author_facet | Jiahua Xing Jiahua Xing Ziqi Jia Yan Li Yan Han |
| author_sort | Jiahua Xing |
| collection | DOAJ |
| description | BackgroundCutaneous melanoma (CM), a kind of skin cancer with a high rate of advanced mortality, exhibits a wide variety of driver and transmitter gene alterations in the immunological tumor microenvironment (TME) associated with tumor cell survival and proliferation.MethodsWe analyzed the immunological infiltration of TME cells in normal and malignant tissues using 469 CM and 556 normal skin samples. We used a single sample gene set enrichment assay (ssGSEA) to quantify the relative abundance of 28 cells, then used the LASSO COX regression model to develop a riskScore prognostic model, followed by a small molecule drug screening and molecular docking validation, which was then validated using qRT-PCR and IHC.ResultsWe developed a prognosis model around seven essential protective genes for the first time, dramatically elevated in tumor tissues, as did immune cell infiltration. Multivariate Cox regression results indicated that riskScore is an independent and robust prognostic indicator, and its predictive value in immunotherapy was verified. Additionally, we identified Gabapentin as a possible small molecule therapeutic for CM.ConclusionsA riskScore model was developed in this work to analyze patient prognosis, TME cell infiltration features, and treatment responsiveness. The development of this model not only aids in predicting patient response to immunotherapy but also has significant implications for the development of novel immunotherapeutic agents and the promotion of tailored treatment regimens. |
| first_indexed | 2024-12-10T09:38:20Z |
| format | Article |
| id | doaj.art-798eca49f09d47928ae306b407b3fb1d |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-10T09:38:20Z |
| publishDate | 2022-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-798eca49f09d47928ae306b407b3fb1d2022-12-22T01:54:07ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-07-011210.3389/fonc.2022.939385939385Construction of immunotherapy-related prognostic gene signature and small molecule drug prediction for cutaneous melanomaJiahua Xing0Jiahua Xing1Ziqi Jia2Yan Li3Yan Han4Department of Plastic and Reconstructive Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing, ChinaSchool of Medicine, Nankai University, Tianjin, ChinaPeking Union Medical College, Chinese Academy of Medical Sciences, Beijing, ChinaDepartment of Plastic and Reconstructive Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing, ChinaDepartment of Plastic and Reconstructive Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing, ChinaBackgroundCutaneous melanoma (CM), a kind of skin cancer with a high rate of advanced mortality, exhibits a wide variety of driver and transmitter gene alterations in the immunological tumor microenvironment (TME) associated with tumor cell survival and proliferation.MethodsWe analyzed the immunological infiltration of TME cells in normal and malignant tissues using 469 CM and 556 normal skin samples. We used a single sample gene set enrichment assay (ssGSEA) to quantify the relative abundance of 28 cells, then used the LASSO COX regression model to develop a riskScore prognostic model, followed by a small molecule drug screening and molecular docking validation, which was then validated using qRT-PCR and IHC.ResultsWe developed a prognosis model around seven essential protective genes for the first time, dramatically elevated in tumor tissues, as did immune cell infiltration. Multivariate Cox regression results indicated that riskScore is an independent and robust prognostic indicator, and its predictive value in immunotherapy was verified. Additionally, we identified Gabapentin as a possible small molecule therapeutic for CM.ConclusionsA riskScore model was developed in this work to analyze patient prognosis, TME cell infiltration features, and treatment responsiveness. The development of this model not only aids in predicting patient response to immunotherapy but also has significant implications for the development of novel immunotherapeutic agents and the promotion of tailored treatment regimens.https://www.frontiersin.org/articles/10.3389/fonc.2022.939385/fullcutaneous melanomatumor microenvironmentprognostic signatureimmunotherapybioinformatics |
| spellingShingle | Jiahua Xing Jiahua Xing Ziqi Jia Yan Li Yan Han Construction of immunotherapy-related prognostic gene signature and small molecule drug prediction for cutaneous melanoma Frontiers in Oncology cutaneous melanoma tumor microenvironment prognostic signature immunotherapy bioinformatics |
| title | Construction of immunotherapy-related prognostic gene signature and small molecule drug prediction for cutaneous melanoma |
| title_full | Construction of immunotherapy-related prognostic gene signature and small molecule drug prediction for cutaneous melanoma |
| title_fullStr | Construction of immunotherapy-related prognostic gene signature and small molecule drug prediction for cutaneous melanoma |
| title_full_unstemmed | Construction of immunotherapy-related prognostic gene signature and small molecule drug prediction for cutaneous melanoma |
| title_short | Construction of immunotherapy-related prognostic gene signature and small molecule drug prediction for cutaneous melanoma |
| title_sort | construction of immunotherapy related prognostic gene signature and small molecule drug prediction for cutaneous melanoma |
| topic | cutaneous melanoma tumor microenvironment prognostic signature immunotherapy bioinformatics |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.939385/full |
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