Experimentally validated oxidative stress -associated prognostic signatures describe the immune landscape and predict the drug response and prognosis of SKCM
BackgroundSkin Cutaneous Melanoma (SKCM) incidence is continually increasing, with chemotherapy and immunotherapy being among the most common cancer treatment modalities. This study aims to identify novel biomarkers for chemotherapy and immunotherapy response in SKCM and explore their association wi...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2024-04-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1387316/full |
| _version_ | 1797215800078106624 |
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| author | Dongyun Rong Yushen Su Dechao Jia Zhirui Zeng Zhirui Zeng Yan Yang Dalong Wei Dalong Wei Honguan Lu Yu Cao |
| author_facet | Dongyun Rong Yushen Su Dechao Jia Zhirui Zeng Zhirui Zeng Yan Yang Dalong Wei Dalong Wei Honguan Lu Yu Cao |
| author_sort | Dongyun Rong |
| collection | DOAJ |
| description | BackgroundSkin Cutaneous Melanoma (SKCM) incidence is continually increasing, with chemotherapy and immunotherapy being among the most common cancer treatment modalities. This study aims to identify novel biomarkers for chemotherapy and immunotherapy response in SKCM and explore their association with oxidative stress.MethodsUtilizing TCGA-SKCM RNA-seq data, we employed Weighted Gene Co-expression Network Analysis (WGCNA) and Protein-Protein Interaction (PPI) networks to identify six core genes. Gene co-expression analysis and immune-related analysis were conducted, and specific markers associated with oxidative stress were identified using Gene Set Variation Analysis (GSVA). Single-cell analysis revealed the expression patterns of Oxidative Stress-Associated Genes (OSAG) in the tumor microenvironment. TIDE analysis was employed to explore the association between immune therapy response and OSAG, while CIBERSORT was used to analyze the tumor immune microenvironment. The BEST database demonstrated the impact of the Oxidative Stress signaling pathway on chemotherapy drug resistance. Immunohistochemical staining and ROC curve evaluation were performed to assess the protein expression levels of core genes in SKCM and normal samples, with survival analysis utilized to determine their diagnostic value.ResultsWe identified six central genes associated with SKCM metastasis, among which the expression of DSC2 and DSC3 involved in the oxidative stress pathway was closely related to immune cell infiltration. DSC2 influenced drug resistance in SKMC patients. Furthermore, downregulation of DSC2 and DSC3 expression enhanced the response of SKCM patients to immunotherapy.ConclusionThis study identified two Oxidative Stress-Associated genes as novel biomarkers for SKCM. Additionally, targeting the oxidative stress pathway may serve as a new strategy in clinical practice to enhance SKCM chemotherapy and sensitivity. |
| first_indexed | 2024-04-24T11:35:49Z |
| format | Article |
| id | doaj.art-00c31725f31e46cbadcca824043937da |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-24T11:35:49Z |
| publishDate | 2024-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-00c31725f31e46cbadcca824043937da2024-04-10T05:16:16ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-04-011510.3389/fimmu.2024.13873161387316Experimentally validated oxidative stress -associated prognostic signatures describe the immune landscape and predict the drug response and prognosis of SKCMDongyun Rong0Yushen Su1Dechao Jia2Zhirui Zeng3Zhirui Zeng4Yan Yang5Dalong Wei6Dalong Wei7Honguan Lu8Yu Cao9Clinical Medical School, Guizhou Medical University, Guiyang, Guizhou, ChinaClinical Medical School, Guizhou Medical University, Guiyang, Guizhou, ChinaClinical Medical School, Guizhou Medical University, Guiyang, Guizhou, ChinaDepartment of anorectal surgery, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, ChinaSchool of Basic Medicine, Guizhou Medical University, Guiyang, Guizhou, ChinaDepartment of Internal Medicine, The Third Affiliated Hospital of Guizhou Medical University, Duyun, Guizhou, ChinaDepartment of Burns, Plastic Surgery and Wound Repair, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi, ChinaKey Laboratory of Tumor Molecular Pathology of Baise, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi, ChinaClinical Medical School, Guizhou Medical University, Guiyang, Guizhou, ChinaClinical Medical School, Guizhou Medical University, Guiyang, Guizhou, ChinaBackgroundSkin Cutaneous Melanoma (SKCM) incidence is continually increasing, with chemotherapy and immunotherapy being among the most common cancer treatment modalities. This study aims to identify novel biomarkers for chemotherapy and immunotherapy response in SKCM and explore their association with oxidative stress.MethodsUtilizing TCGA-SKCM RNA-seq data, we employed Weighted Gene Co-expression Network Analysis (WGCNA) and Protein-Protein Interaction (PPI) networks to identify six core genes. Gene co-expression analysis and immune-related analysis were conducted, and specific markers associated with oxidative stress were identified using Gene Set Variation Analysis (GSVA). Single-cell analysis revealed the expression patterns of Oxidative Stress-Associated Genes (OSAG) in the tumor microenvironment. TIDE analysis was employed to explore the association between immune therapy response and OSAG, while CIBERSORT was used to analyze the tumor immune microenvironment. The BEST database demonstrated the impact of the Oxidative Stress signaling pathway on chemotherapy drug resistance. Immunohistochemical staining and ROC curve evaluation were performed to assess the protein expression levels of core genes in SKCM and normal samples, with survival analysis utilized to determine their diagnostic value.ResultsWe identified six central genes associated with SKCM metastasis, among which the expression of DSC2 and DSC3 involved in the oxidative stress pathway was closely related to immune cell infiltration. DSC2 influenced drug resistance in SKMC patients. Furthermore, downregulation of DSC2 and DSC3 expression enhanced the response of SKCM patients to immunotherapy.ConclusionThis study identified two Oxidative Stress-Associated genes as novel biomarkers for SKCM. Additionally, targeting the oxidative stress pathway may serve as a new strategy in clinical practice to enhance SKCM chemotherapy and sensitivity.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1387316/fullSKCMoxidative stress networkimmunotherapy responsedrug resistanceimmune |
| spellingShingle | Dongyun Rong Yushen Su Dechao Jia Zhirui Zeng Zhirui Zeng Yan Yang Dalong Wei Dalong Wei Honguan Lu Yu Cao Experimentally validated oxidative stress -associated prognostic signatures describe the immune landscape and predict the drug response and prognosis of SKCM Frontiers in Immunology SKCM oxidative stress network immunotherapy response drug resistance immune |
| title | Experimentally validated oxidative stress -associated prognostic signatures describe the immune landscape and predict the drug response and prognosis of SKCM |
| title_full | Experimentally validated oxidative stress -associated prognostic signatures describe the immune landscape and predict the drug response and prognosis of SKCM |
| title_fullStr | Experimentally validated oxidative stress -associated prognostic signatures describe the immune landscape and predict the drug response and prognosis of SKCM |
| title_full_unstemmed | Experimentally validated oxidative stress -associated prognostic signatures describe the immune landscape and predict the drug response and prognosis of SKCM |
| title_short | Experimentally validated oxidative stress -associated prognostic signatures describe the immune landscape and predict the drug response and prognosis of SKCM |
| title_sort | experimentally validated oxidative stress associated prognostic signatures describe the immune landscape and predict the drug response and prognosis of skcm |
| topic | SKCM oxidative stress network immunotherapy response drug resistance immune |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1387316/full |
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