An original cuproptosis-related genes signature effectively influences the prognosis and immune status of head and neck squamous cell carcinoma
Background: Recently, a non-apoptotic cell death pathway that is dependent on the presence of copper ions was proposed, named as cuproptosis. Cuproptosis have been found to have a strong association with the clinical progression and prognosis of several cancers. Head and neck squamous cell carcinoma...
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Frontiers Media S.A.
2023-01-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2022.1084206/full |
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| author | Xiwang Zheng Xiwang Zheng Chunming Zhang Chunming Zhang Chunming Zhang Defei Zheng Qingbo Guo Qingbo Guo Mijiti Maierhaba Mijiti Maierhaba Lingbin Xue Lingbin Xue Xianhai Zeng Xianhai Zeng Yongyan Wu Yongyan Wu Wei Gao Wei Gao |
| author_facet | Xiwang Zheng Xiwang Zheng Chunming Zhang Chunming Zhang Chunming Zhang Defei Zheng Qingbo Guo Qingbo Guo Mijiti Maierhaba Mijiti Maierhaba Lingbin Xue Lingbin Xue Xianhai Zeng Xianhai Zeng Yongyan Wu Yongyan Wu Wei Gao Wei Gao |
| author_sort | Xiwang Zheng |
| collection | DOAJ |
| description | Background: Recently, a non-apoptotic cell death pathway that is dependent on the presence of copper ions was proposed, named as cuproptosis. Cuproptosis have been found to have a strong association with the clinical progression and prognosis of several cancers. Head and neck squamous cell carcinoma (HNSC) are among the most common malignant tumors, with a 5-year relative survival rate ranging between 40% and 50%. The underlying mechanisms and clinical significance of cuproptosis-related genes (CRGs) in HNSC progression have not been clarified.Methods: In this study, expression pattern, biological functions, Immunohistochemistry (IHC), gene variants and immune status were analyzed to investigate the effects of CRGs on HNSC progression. Moreover, a 12-CRGs signature and nomogram were also constructed for prognosis prediction of HNSC.Results: The results revealed that some CRGs were dysregulated, had somatic mutations, and CNV in HNSC tissues. Among them, ISCA2 was found to be upregulated in HNSC and was strongly correlated with the overall survival (OS) of HNSC patients (HR = 1.13 [1.01–1.26], p-value = 0.0331). Functionally, CRGs was mainly associated with the TCA cycle, cell cycle, iron-sulfur cluster assembly, p53 signaling pathway, chemical carcinogenesis, and carbon metabolism in cancer. A 12-CRGs signature for predicting the OS was constructed which included, CAT, MTFR1L, OXA1L, POLE, NTHL1, DNA2, ATP7B, ISCA2, GLRX5, NDUFA1, and NDUFB2. This signature showed good prediction performance on the OS (HR = 5.3 [3.4–8.2], p-value = 3.4e-13) and disease-specific survival (HR = 6.4 [3.6–11], p-value = 2.4e-10). Furthermore, 12-CRGs signature significantly suppressed the activation of CD4+ T cells and antigen processing and presentation. Finally, a nomogram based on a 12-CRGs signature and clinical features was constructed which showed a significantly adverse effect on OS (HR = 1.061 [1.042–1.081], p-value = 1.6e-10) of HNSC patients.Conclusion: This study reveals the association of CRGs with the progression of HNSC based on multi-omics analysis. The study of CRGs is expected to improve clinical diagnosis, immunotherapeutic responsiveness and prognosis prediction of HNSC. |
| first_indexed | 2024-04-11T01:05:40Z |
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| last_indexed | 2024-04-11T01:05:40Z |
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| spelling | doaj.art-c34eb9bfdc95499b8ee465b233f7e3242023-01-04T13:24:06ZengFrontiers Media S.A.Frontiers in Genetics1664-80212023-01-011310.3389/fgene.2022.10842061084206An original cuproptosis-related genes signature effectively influences the prognosis and immune status of head and neck squamous cell carcinomaXiwang Zheng0Xiwang Zheng1Chunming Zhang2Chunming Zhang3Chunming Zhang4Defei Zheng5Qingbo Guo6Qingbo Guo7Mijiti Maierhaba8Mijiti Maierhaba9Lingbin Xue10Lingbin Xue11Xianhai Zeng12Xianhai Zeng13Yongyan Wu14Yongyan Wu15Wei Gao16Wei Gao17Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, First Hospital of Shanxi Medical University, Taiyuan, Shanxi, ChinaShanxi Province Clinical Medical Research Center for Precision Medicine of Head and Neck Cancer, First Hospital of Shanxi Medical University, Taiyuan, Shanxi, ChinaShanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, First Hospital of Shanxi Medical University, Taiyuan, Shanxi, ChinaShanxi Province Clinical Medical Research Center for Precision Medicine of Head and Neck Cancer, First Hospital of Shanxi Medical University, Taiyuan, Shanxi, ChinaDepartment of Otolaryngology Head and Neck Surgery, First Hospital of Shanxi Medical University, Taiyuan, Shanxi, ChinaDepartment of Hematology/Oncology, Children’s Hospital of Soochow University, Suzhou, Jiangsu, ChinaShanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, First Hospital of Shanxi Medical University, Taiyuan, Shanxi, ChinaShanxi Province Clinical Medical Research Center for Precision Medicine of Head and Neck Cancer, First Hospital of Shanxi Medical University, Taiyuan, Shanxi, ChinaShanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, First Hospital of Shanxi Medical University, Taiyuan, Shanxi, ChinaShanxi Province Clinical Medical Research Center for Precision Medicine of Head and Neck Cancer, First Hospital of Shanxi Medical University, Taiyuan, Shanxi, ChinaDepartment of Otolaryngology Head and Neck Surgery, Longgang Otolaryngology Hospital, Shenzhen, Guangdong, ChinaShenzhen Institute of Otolaryngology and Key Laboratory of Otolaryngology, Longgang Otolaryngology Hospital, Shenzhen, Guangdong, ChinaDepartment of Otolaryngology Head and Neck Surgery, Longgang Otolaryngology Hospital, Shenzhen, Guangdong, ChinaShenzhen Institute of Otolaryngology and Key Laboratory of Otolaryngology, Longgang Otolaryngology Hospital, Shenzhen, Guangdong, ChinaDepartment of Otolaryngology Head and Neck Surgery, Longgang Otolaryngology Hospital, Shenzhen, Guangdong, ChinaShenzhen Institute of Otolaryngology and Key Laboratory of Otolaryngology, Longgang Otolaryngology Hospital, Shenzhen, Guangdong, ChinaDepartment of Otolaryngology Head and Neck Surgery, Longgang Otolaryngology Hospital, Shenzhen, Guangdong, ChinaShenzhen Institute of Otolaryngology and Key Laboratory of Otolaryngology, Longgang Otolaryngology Hospital, Shenzhen, Guangdong, ChinaBackground: Recently, a non-apoptotic cell death pathway that is dependent on the presence of copper ions was proposed, named as cuproptosis. Cuproptosis have been found to have a strong association with the clinical progression and prognosis of several cancers. Head and neck squamous cell carcinoma (HNSC) are among the most common malignant tumors, with a 5-year relative survival rate ranging between 40% and 50%. The underlying mechanisms and clinical significance of cuproptosis-related genes (CRGs) in HNSC progression have not been clarified.Methods: In this study, expression pattern, biological functions, Immunohistochemistry (IHC), gene variants and immune status were analyzed to investigate the effects of CRGs on HNSC progression. Moreover, a 12-CRGs signature and nomogram were also constructed for prognosis prediction of HNSC.Results: The results revealed that some CRGs were dysregulated, had somatic mutations, and CNV in HNSC tissues. Among them, ISCA2 was found to be upregulated in HNSC and was strongly correlated with the overall survival (OS) of HNSC patients (HR = 1.13 [1.01–1.26], p-value = 0.0331). Functionally, CRGs was mainly associated with the TCA cycle, cell cycle, iron-sulfur cluster assembly, p53 signaling pathway, chemical carcinogenesis, and carbon metabolism in cancer. A 12-CRGs signature for predicting the OS was constructed which included, CAT, MTFR1L, OXA1L, POLE, NTHL1, DNA2, ATP7B, ISCA2, GLRX5, NDUFA1, and NDUFB2. This signature showed good prediction performance on the OS (HR = 5.3 [3.4–8.2], p-value = 3.4e-13) and disease-specific survival (HR = 6.4 [3.6–11], p-value = 2.4e-10). Furthermore, 12-CRGs signature significantly suppressed the activation of CD4+ T cells and antigen processing and presentation. Finally, a nomogram based on a 12-CRGs signature and clinical features was constructed which showed a significantly adverse effect on OS (HR = 1.061 [1.042–1.081], p-value = 1.6e-10) of HNSC patients.Conclusion: This study reveals the association of CRGs with the progression of HNSC based on multi-omics analysis. The study of CRGs is expected to improve clinical diagnosis, immunotherapeutic responsiveness and prognosis prediction of HNSC.https://www.frontiersin.org/articles/10.3389/fgene.2022.1084206/fullhead and neck squamous cell carcinomacuproptosisISCA2immune infiltrationprognosis |
| spellingShingle | Xiwang Zheng Xiwang Zheng Chunming Zhang Chunming Zhang Chunming Zhang Defei Zheng Qingbo Guo Qingbo Guo Mijiti Maierhaba Mijiti Maierhaba Lingbin Xue Lingbin Xue Xianhai Zeng Xianhai Zeng Yongyan Wu Yongyan Wu Wei Gao Wei Gao An original cuproptosis-related genes signature effectively influences the prognosis and immune status of head and neck squamous cell carcinoma Frontiers in Genetics head and neck squamous cell carcinoma cuproptosis ISCA2 immune infiltration prognosis |
| title | An original cuproptosis-related genes signature effectively influences the prognosis and immune status of head and neck squamous cell carcinoma |
| title_full | An original cuproptosis-related genes signature effectively influences the prognosis and immune status of head and neck squamous cell carcinoma |
| title_fullStr | An original cuproptosis-related genes signature effectively influences the prognosis and immune status of head and neck squamous cell carcinoma |
| title_full_unstemmed | An original cuproptosis-related genes signature effectively influences the prognosis and immune status of head and neck squamous cell carcinoma |
| title_short | An original cuproptosis-related genes signature effectively influences the prognosis and immune status of head and neck squamous cell carcinoma |
| title_sort | original cuproptosis related genes signature effectively influences the prognosis and immune status of head and neck squamous cell carcinoma |
| topic | head and neck squamous cell carcinoma cuproptosis ISCA2 immune infiltration prognosis |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2022.1084206/full |
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