BRD4抑制剂JQ1可能通过超增强子相关基因影响宫颈癌预后

IF 0.5 4区 医学 Q4 OBSTETRICS & GYNECOLOGY European journal of gynaecological oncology Pub Date : 2023-01-01 DOI:10.22514/ejgo.2023.076
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引用次数: 0

摘要

为探讨溴结构域蛋白4 (BRD4)抑制剂JQ1对宫颈癌(CC) HeLa细胞中超增强子相关基因(se基因)表达谱的影响,构建预后模型,探讨JQ1对CC预后的潜在影响,采用全转录组测序技术检测JQ1处理和对照细胞的基因表达谱变化。通过dbCoRC数据库和Cistrome数据浏览器(Cistrome DB)进行比对,鉴定出差异表达的se基因。在肿瘤基因组图谱(Cancer Genome Atlas, TCGA)数据集中,基于基因表达状态分析se基因差异表达的预后。采用Cox比例风险模型和最小绝对收缩和选择算子(LASSO)回归构建预后模型。从dbCoRC和Cistrome DB中共鉴定出1161个se基因,其中1004个se基因与JQ1转录组测序的表达谱成功匹配。差异表达分析鉴定出110个se基因差异表达,其中72个se基因下调,38个se基因上调。然后构建9 se基因预后模型,Kaplan-Meier (K-M)曲线显示,高危组临床生存结局明显较差(p <0.05)。随时间变化的受试者工作特征(ROC)曲线显示,该模型的1年、2年和3年生存估计分别为0.82、0.86和0.87,表现出良好的性能。JQ1显著影响HeLa细胞se基因表达谱,基于9个se基因差异表达的模型可以有效预测CC患者的生存结局。由于本研究基于探索性分析,需要进一步的前瞻性研究
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BRD4 inhibitor JQ1 may affect the prognosis of cervical cancer through super-enhancer-related genes
To explore the effects of bromine domain protein 4 (BRD4) inhibitor JQ1 on the expression profile of super-enhancer-related genes (SE-genes) in cervical cancer (CC) HeLa cells and construct a prognosis model to explore the potential impact of JQ1 on the prognosis of CC. Whole transcriptome sequencing technology was used to detect changes in the gene expression profiles of JQ1-treated and control cells. Differentially expressed SE-genes were identified by matching via the dbCoRC database and Cistrome Data Browser (Cistrome DB). The prognosis of differentially expressed SE-genes was analyzed in the Cancer Genome Atlas (TCGA) dataset based on gene expression status. The Cox proportional risk model and least absolute shrinkage and selection operator (LASSO) regression were used to construct the prognostic model. A total of 1161 SE-genes were identified from dbCoRC and Cistrome DB, among which 1004 SE-genes were successfully matched to the expression profiles of JQ1 transcriptome sequencing. Differential expression analysis identified 110 differentially expressed SE-genes, among which 72 were down-regulated and 38 were upregulated. Then, a 9 SE-gene prognostic model was constructed, and Kaplan-Meier (K-M) curves showed that the high-risk group had significantly poorer clinical survival outcomes (p < 0.05). Time-dependent receiver operating characteristic (ROC) curves showed that the 1-year, 2-year and 3-year survival estimation of the proposed model was 0.82, 0.86 and 0.87, respectively, demonstrating excellent performance. JQ1 significantly impacts the SE-genes expression profile of HeLa cells, and the proposed model based on 9 differentially expressed SE-genes may effectively predict the survival outcomes of CC patients. As this study was based on exploratory analysis, further prospective studies are needed to v
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来源期刊
自引率
25.00%
发文量
58
审稿时长
1 months
期刊介绍: EJGO is dedicated to publishing editorial articles in the Distinguished Expert Series and original research papers, case reports, letters to the Editor, book reviews, and newsletters. The Journal was founded in 1980 the second gynaecologic oncology hyperspecialization Journal in the world. Its aim is the diffusion of scientific, clinical and practical progress, and knowledge in female neoplastic diseases in an interdisciplinary approach among gynaecologists, oncologists, radiotherapists, surgeons, chemotherapists, pathologists, epidemiologists, and so on.
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