Identification of a chromatin regulator signature and potential candidate drugs for bladder cancer.
Identification of a chromatin regulator signature and potential candidate drugs for bladder cancer.
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DOI：
10.1186/s41065-021-00212-x
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发表时间：
2022-02-07
期刊：
影响因子：
2.7
通讯作者：
Fu B
中科院分区：
文献类型：
--
作者：
Zhu K;Liu X;Deng W;Wang G;Fu B
膀胱癌(BLCA)是一种结果令人沮丧的恶性肿瘤。越来越多的证据证实染色质调节剂(CRS)参与了癌症的进展。因此，我们旨在探讨CRS在BLCA患者中的作用和预后价值。染色质调节剂(CRS)是从先前的顶级研究中获得的。从TCGA和GEO数据集中下载基因表达和临床信息。用COX回归分析和最小绝对收缩选择算子(LASSO)回归分析筛选预后基因，建立预测预后的风险模型。Kaplan-Meier分析用于评估高危组和低危组之间的预后。我们还调查了高风险组和低风险组之间的药物敏感性差异。使用CMAP数据集筛选小分子药物进行治疗。我们成功地构建并验证了一个基于11CRS的预测BLCA患者预后的模型。此外，我们还发现11个基于CRS的模型是一个独立的预后因素。功能分析表明，CRS主要在与癌症相关的信号通路中富含。CR模型还与免疫细胞浸润和免疫检查点相关。高危组患者对丝裂霉素C、吉西他滨、顺铂等药物更为敏感。8种小分子药物可能对BLCA患者的治疗有利。综上所述，我们的研究为CRS在BLCA中的作用提供了新的见解。我们确定了BLCA患者生存的一个可靠的预后生物标志物。网上版载有补充材料，可在10.1186/s41065.021-00212-x查阅。
Bladder cancer (BLCA) is a malignant tumor with a dismay outcome. Increasing evidence has confirmed that chromatin regulators (CRs) are involved in cancer progression. Therefore, we aimed to explore the function and prognostic value of CRs in BLCA patients. Chromatin regulators (CRs) were acquired from the previous top research. The mRNA expression and clinical information were downloaded from TCGA and GEO datasets. Cox regression analysis and least absolute shrinkage and selection operator (LASSO) regression analysis were performed to select the prognostic gene and construct the risk model for predicting outcome in BLCA. The Kaplan-Meier analysis was used to assess the prognosis between high- and low-risk groups. We also investigated the drug sensitivity difference between high- and low-risk groups. CMAP dataset was performed to screen the small molecule drugs for treatment. We successfully constructed and validated an 11 CRs-based model for predicting the prognosis of patients with BLCA. Moreover, we also found 11 CRs-based model was an independent prognostic factor. Functional analysis suggested that CRs were mainly enriched in cancer-related signaling pathways. The CR-based model was also correlated with immune cells infiltration and immune checkpoint. Patients in the high-risk group were more sensitive to several drugs, such as mitomycin C, gemcitabine, cisplatin. Eight small molecule drugs could be beneficial to treatment for BLCA patients. In conclusion, our study provided novel insights into the function of CRs in BLCA. We identified a reliable prognostic biomarker for the survival of patients with BLCA. The online version contains supplementary material available at 10.1186/s41065-021-00212-x.
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