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CDC6 is a prognostic biomarker and correlated with immune infiltrates in glioma
BACKGROUND: Cell division cycle 6 (CDC6) has been proven to be associated with the initiation and progression of human multiple tumors. However, it’s role in glioma, which is ranked as one of the common primary malignant tumor in the central nervous system and is associated with high morbidity and m...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9316328/ https://www.ncbi.nlm.nih.gov/pubmed/35879762 http://dx.doi.org/10.1186/s12943-022-01623-8 |
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author | Wang, Feng Zhao, Fen Zhang, Li Xiong, Lai Mao, Qing Liu, Yanhui Qiu, Xiaoguang Wang, Xiang Shui, Lin Chen, Xi Ren, Kexing Shui, Pixian Zhang, Qiongwen Deng, Yifei Li, Weimin Xie, Xiaoqi Wu, Dengbin Li, Tao Lang, Jinyi Liu, Lei Chen, Huaying Xu, Jianguo Bai, Sen Li, Zhiping Yue, Qiang Chen, Ni Zhou, Bingwen Yi, Cheng Wei, Yuquan Fu, Yuchuan Luo, Yong Gou, Qiheng Liu, Lunxu Liu, Yuanzhao Kang, Jingbo Wang, Junjie Jing, Dongcun Zhang, Fuquan Yang, Xiaoyan Li, Xianfeng Jiang, Tao Zhang, Zongcun Zhou, Yizhi Yi, Junlin |
author_facet | Wang, Feng Zhao, Fen Zhang, Li Xiong, Lai Mao, Qing Liu, Yanhui Qiu, Xiaoguang Wang, Xiang Shui, Lin Chen, Xi Ren, Kexing Shui, Pixian Zhang, Qiongwen Deng, Yifei Li, Weimin Xie, Xiaoqi Wu, Dengbin Li, Tao Lang, Jinyi Liu, Lei Chen, Huaying Xu, Jianguo Bai, Sen Li, Zhiping Yue, Qiang Chen, Ni Zhou, Bingwen Yi, Cheng Wei, Yuquan Fu, Yuchuan Luo, Yong Gou, Qiheng Liu, Lunxu Liu, Yuanzhao Kang, Jingbo Wang, Junjie Jing, Dongcun Zhang, Fuquan Yang, Xiaoyan Li, Xianfeng Jiang, Tao Zhang, Zongcun Zhou, Yizhi Yi, Junlin |
author_sort | Wang, Feng |
collection | PubMed |
description | BACKGROUND: Cell division cycle 6 (CDC6) has been proven to be associated with the initiation and progression of human multiple tumors. However, it’s role in glioma, which is ranked as one of the common primary malignant tumor in the central nervous system and is associated with high morbidity and mortality, is unclear. METHODS: In this study, we explored CDC6 gene expression level in pan-cancer. Furthermore, we focused on the relationships between CDC6 expression, its prognostic value, potential biological functions, and immune infiltrates in glioma patients. We also performed vitro experiments to assess the effect of CDC6 expression on proliferative, apoptotic, migrant and invasive abilities of glioma cells. RESULTS: As a result, CDC6 expression was upregulated in multiple types of cancer, including glioma. Moreover, high expression of CDC6 was significantly associated with age, IDH status, 1p/19q codeletion status, WHO grade and histological type in glioma (all p < 0.05). Meanwhile, high CDC6 expression was associated with poor overall survival (OS) in glioma patients, especially in different clinical subgroups. Furthermore, a univariate Cox analysis showed that high CDC6 expression was correlated with poor OS in glioma patients. Functional enrichment analysis indicated that CDC6 was mainly involved in pathways related to DNA transcription and cytokine activity, and Gene Set Enrichment Analysis (GSEA) revealed that MAPK pathway, P53 pathway and NF-κB pathway in cancer were differentially enriched in glioma patients with high CDC6 expression. Single-sample gene set enrichment analysis (ssGSEA) showed CDC6 expression in glioma was positively correlated with Th2 cells, Macrophages and Eosinophils, and negative correlations with plasmacytoid dendritic cells, CD8 T cells and NK CD56bright cells, suggesting its role in regulating tumor immunity. Finally, CCK8 assay, flow cytometry and transwell assays showed that silencing CDC6 could significantly inhibit proliferation, migration, invasion, and promoted apoptosis of U87 cells and U251 cells (p < 0.05). CONCLUSION: In conclusion, high CDC6 expression may serve as a promising biomarker for prognosis and correlated with immune infiltrates, presenting to be a potential immune therapy target in glioma. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12943-022-01623-8. |
format | Online Article Text |
id | pubmed-9316328 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-93163282022-07-27 CDC6 is a prognostic biomarker and correlated with immune infiltrates in glioma Wang, Feng Zhao, Fen Zhang, Li Xiong, Lai Mao, Qing Liu, Yanhui Qiu, Xiaoguang Wang, Xiang Shui, Lin Chen, Xi Ren, Kexing Shui, Pixian Zhang, Qiongwen Deng, Yifei Li, Weimin Xie, Xiaoqi Wu, Dengbin Li, Tao Lang, Jinyi Liu, Lei Chen, Huaying Xu, Jianguo Bai, Sen Li, Zhiping Yue, Qiang Chen, Ni Zhou, Bingwen Yi, Cheng Wei, Yuquan Fu, Yuchuan Luo, Yong Gou, Qiheng Liu, Lunxu Liu, Yuanzhao Kang, Jingbo Wang, Junjie Jing, Dongcun Zhang, Fuquan Yang, Xiaoyan Li, Xianfeng Jiang, Tao Zhang, Zongcun Zhou, Yizhi Yi, Junlin Mol Cancer Correspondence BACKGROUND: Cell division cycle 6 (CDC6) has been proven to be associated with the initiation and progression of human multiple tumors. However, it’s role in glioma, which is ranked as one of the common primary malignant tumor in the central nervous system and is associated with high morbidity and mortality, is unclear. METHODS: In this study, we explored CDC6 gene expression level in pan-cancer. Furthermore, we focused on the relationships between CDC6 expression, its prognostic value, potential biological functions, and immune infiltrates in glioma patients. We also performed vitro experiments to assess the effect of CDC6 expression on proliferative, apoptotic, migrant and invasive abilities of glioma cells. RESULTS: As a result, CDC6 expression was upregulated in multiple types of cancer, including glioma. Moreover, high expression of CDC6 was significantly associated with age, IDH status, 1p/19q codeletion status, WHO grade and histological type in glioma (all p < 0.05). Meanwhile, high CDC6 expression was associated with poor overall survival (OS) in glioma patients, especially in different clinical subgroups. Furthermore, a univariate Cox analysis showed that high CDC6 expression was correlated with poor OS in glioma patients. Functional enrichment analysis indicated that CDC6 was mainly involved in pathways related to DNA transcription and cytokine activity, and Gene Set Enrichment Analysis (GSEA) revealed that MAPK pathway, P53 pathway and NF-κB pathway in cancer were differentially enriched in glioma patients with high CDC6 expression. Single-sample gene set enrichment analysis (ssGSEA) showed CDC6 expression in glioma was positively correlated with Th2 cells, Macrophages and Eosinophils, and negative correlations with plasmacytoid dendritic cells, CD8 T cells and NK CD56bright cells, suggesting its role in regulating tumor immunity. Finally, CCK8 assay, flow cytometry and transwell assays showed that silencing CDC6 could significantly inhibit proliferation, migration, invasion, and promoted apoptosis of U87 cells and U251 cells (p < 0.05). CONCLUSION: In conclusion, high CDC6 expression may serve as a promising biomarker for prognosis and correlated with immune infiltrates, presenting to be a potential immune therapy target in glioma. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12943-022-01623-8. BioMed Central 2022-07-25 /pmc/articles/PMC9316328/ /pubmed/35879762 http://dx.doi.org/10.1186/s12943-022-01623-8 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Correspondence Wang, Feng Zhao, Fen Zhang, Li Xiong, Lai Mao, Qing Liu, Yanhui Qiu, Xiaoguang Wang, Xiang Shui, Lin Chen, Xi Ren, Kexing Shui, Pixian Zhang, Qiongwen Deng, Yifei Li, Weimin Xie, Xiaoqi Wu, Dengbin Li, Tao Lang, Jinyi Liu, Lei Chen, Huaying Xu, Jianguo Bai, Sen Li, Zhiping Yue, Qiang Chen, Ni Zhou, Bingwen Yi, Cheng Wei, Yuquan Fu, Yuchuan Luo, Yong Gou, Qiheng Liu, Lunxu Liu, Yuanzhao Kang, Jingbo Wang, Junjie Jing, Dongcun Zhang, Fuquan Yang, Xiaoyan Li, Xianfeng Jiang, Tao Zhang, Zongcun Zhou, Yizhi Yi, Junlin CDC6 is a prognostic biomarker and correlated with immune infiltrates in glioma |
title | CDC6 is a prognostic biomarker and correlated with immune infiltrates in glioma |
title_full | CDC6 is a prognostic biomarker and correlated with immune infiltrates in glioma |
title_fullStr | CDC6 is a prognostic biomarker and correlated with immune infiltrates in glioma |
title_full_unstemmed | CDC6 is a prognostic biomarker and correlated with immune infiltrates in glioma |
title_short | CDC6 is a prognostic biomarker and correlated with immune infiltrates in glioma |
title_sort | cdc6 is a prognostic biomarker and correlated with immune infiltrates in glioma |
topic | Correspondence |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9316328/ https://www.ncbi.nlm.nih.gov/pubmed/35879762 http://dx.doi.org/10.1186/s12943-022-01623-8 |
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