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Integrative Analysis of Genetic and Epigenetic Alterations in the CBX7 Gene Reveals Its Tumor-Suppressive Function by Regulating the Cell Cycle in Human Breast Cancer CBX7基因的遗传和表观遗传改变的综合分析通过调节人类乳腺癌细胞周期揭示其肿瘤抑制功能
Pub Date : 2023-01-01 DOI: 10.55085/oi.2023.691
Yimeng Cai, Hang Chang, J. Pérez-Losada, J. Mao
CBX7 is a member of the chromobox gene family, which plays an important role in epigenetic transcriptional regulation. In this study, we found that compared to normal mammary tissues, mRNA levels of CBX7 are consistently significantly downregulated in breast cancers (BCs) across different datasets. Integrative multiomics analysis revealed the genetic and epigenetic mechanisms for the loss of CBX7 expression in BCs. Lower expression levels of CBX7 are significantly associated with shorter overall, disease-free, and distant metastasis-free survival of patients with BC. These prognostic impacts of CBX7 are independent of estrogen receptor status and PAM50 molecular subtypes. Coexpression analysis identified 207 genes consistently coexpressed with CBX7 (157 negatively and 50 positively). Gene Ontology, KEGG, and Reactome enrichment analysis revealed that cell cycle‑, DNA replication‑, and mitosis-related pathways are significantly overrepresented within the set of CBX7 negatively coexpressed genes, suggesting that CBX7 functions as a suppressor of the cell cycle. Moreover, transcription factor enrichment analysis detected the E2F family of transcription factors significantly associated with CBX7 negatively coexpressed genes, consistent with E2F function regulating the cell cycle. Furthermore, we found that loss of CBX7 expression significantly increases genomic instability and tumor mutation burden. Our findings indicate that CBX7 acts as a tumor suppressor in BC through its potential role in the negative regulation of cell proliferation and the maintenance of genome integrity.
CBX7是染色体盒基因家族的一员,在表观遗传转录调控中起重要作用。在这项研究中,我们发现与正常乳腺组织相比,不同数据集的乳腺癌(bc)中CBX7 mRNA水平一致显著下调。综合多组学分析揭示了CBX7在bc中表达缺失的遗传和表观遗传机制。较低的CBX7表达水平与BC患者较短的总体无病和远端无转移生存期显著相关。CBX7的这些预后影响与雌激素受体状态和PAM50分子亚型无关。共表达分析发现207个基因与CBX7一致共表达(157个为阴性,50个为阳性)。基因本体、KEGG和Reactome富集分析显示,在CBX7负共表达基因集中,细胞周期、DNA复制和有丝分裂相关途径显著过度表达,表明CBX7作为细胞周期的抑制因子。此外,转录因子富集分析检测到E2F家族转录因子与CBX7负共表达基因显著相关,符合E2F调节细胞周期的功能。此外,我们发现CBX7表达的缺失显著增加了基因组不稳定性和肿瘤突变负担。我们的研究结果表明,CBX7通过其潜在的负调控细胞增殖和维持基因组完整性的作用,在BC中发挥肿瘤抑制作用。
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引用次数: 0
Exploring the epigenetics of the TME 探索TME的表观遗传学
Pub Date : 2022-12-19 DOI: 10.18609/ioi.2022.045
Jesús M Paramio
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引用次数: 0
Modulation of both tumor & T cell apoptosis to enhance CAR-T immunotherapy 调节肿瘤和T细胞凋亡以增强CAR-T免疫治疗
Pub Date : 2022-12-19 DOI: 10.18609/ioi.2022.053
M. Ruella
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引用次数: 0
Emerging characterization of the tumor-restraining subset of CAFs CAFs肿瘤抑制亚群的新特征
Pub Date : 2022-12-19 DOI: 10.18609/ioi.2022.046
Jamie Bates
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引用次数: 0
Studying the tumor microenvironment under pressure 压力下肿瘤微环境的研究
Pub Date : 2022-12-19 DOI: 10.18609/ioi.2022.039
Meenal Datta
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引用次数: 0
Immune modulatory vaccines: the safe way to inflame the tumor microenvironment & guide anti-cancer immunotherapies 免疫调节疫苗:安全激活肿瘤微环境,引导抗癌免疫治疗
Pub Date : 2022-12-19 DOI: 10.18609/ioi.2022.043
M. Hald Andersen
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引用次数: 0
Predicting patient response to immune-targeted therapies via interrogation of the tumor microenvironment 通过询问肿瘤微环境预测患者对免疫靶向治疗的反应
Pub Date : 2022-12-19 DOI: 10.18609/ioi.2022.052
M. Uhlik, Dr Caroline Fong
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引用次数: 0
Exploring approaches for tackling the complexity of the tumor microenvironment: multi-parametric methods, new biomarkers & serial testing 探索解决肿瘤微环境复杂性的方法:多参数方法,新的生物标志物和系列测试
Pub Date : 2022-12-19 DOI: 10.18609/ioi.2022.047
L. Benjamin, M. Uhlik
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引用次数: 0
Shifting paradigms & advancing technology to find I–O biomarkers 转变范式和推进技术以寻找I/O生物标志物
Pub Date : 2022-12-15 DOI: 10.18609/ioi.2022.055
M. Khasraw
{"title":"Shifting paradigms & advancing technology to find I–O biomarkers","authors":"M. Khasraw","doi":"10.18609/ioi.2022.055","DOIUrl":"https://doi.org/10.18609/ioi.2022.055","url":null,"abstract":"","PeriodicalId":73351,"journal":{"name":"Immuno-oncology insights","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47859456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The changing landscape of cancer vaccines: developing in situ vaccination 癌症疫苗的变化前景:发展原位疫苗接种
Pub Date : 2022-12-15 DOI: 10.18609/ioi.2022.054
J. Brody
{"title":"The changing landscape of cancer vaccines: developing in situ vaccination","authors":"J. Brody","doi":"10.18609/ioi.2022.054","DOIUrl":"https://doi.org/10.18609/ioi.2022.054","url":null,"abstract":"","PeriodicalId":73351,"journal":{"name":"Immuno-oncology insights","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44572815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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Immuno-oncology insights
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