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全面分析组蛋白去乙酰化酶基因在胶质瘤患者预后和免疫浸润中的作用。

Comprehensive analysis of histone deacetylases genes in the prognosis and immune infiltration of glioma patients.

机构信息

Department of Oncology, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, PR China.

Department of Nursing, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, PR China.

出版信息

Aging (Albany NY). 2022 May 11;14(9):4050-4068. doi: 10.18632/aging.204071.

Abstract

The occurrence and development of tumors are closely related to histone deacetylases (HDACs). However, their relationship with the overall biology and prognosis of glioma is still unknown. In the present study, we developed and validated a prognostic model for glioma based on HDAC genes. Glioma patients can be divided into two subclasses based on eleven HDAC genes, and patients from the two subclasses had markedly different survival outcomes. Then, using six HDAC genes (HDAC1, HDAC3, HDAC4, HDAC5, HDAC7, and HDAC9), we established a prognostic model for glioma patients, and this prognostic model was validated in an independent cohort. Furthermore, the calculated risk score from six HDACA genes expression was found to be an independent prognostic factor that could predict the five-year overall survival of glioma patients well. High-risk patients have changes in multiple complex functions and molecular signaling pathways, and the gene alterations of high- and low-risk patients were significantly different. We also found that the different survival outcomes of high- and low-risk patients could be related to the differences in immune filtration levels and the tumor microenvironment. Subsequently, we identified several small molecular compounds that could be favorable for glioma patient treatment. Finally, the expression levels of HDAC genes from the prognostic model were validated in glioma and nontumor tissue samples. Our results revealed the clinical utility and potential molecular mechanisms of HDAC genes in glioma. A model based on six HDAC genes can predict the overall survival of glioma patients well, and these genes are potential therapeutic targets.

摘要

肿瘤的发生和发展与组蛋白去乙酰化酶(HDACs)密切相关。然而,它们与神经胶质瘤的整体生物学和预后的关系尚不清楚。在本研究中,我们基于 HDAC 基因开发并验证了一种神经胶质瘤的预后模型。根据十一个 HDAC 基因,将神经胶质瘤患者分为两个亚类,这两个亚类的患者具有明显不同的生存结局。然后,使用六个 HDAC 基因(HDAC1、HDAC3、HDAC4、HDAC5、HDAC7 和 HDAC9),我们建立了神经胶质瘤患者的预后模型,并在独立队列中进行了验证。此外,六个 HDACA 基因表达计算出的风险评分被发现是一个独立的预后因素,可以很好地预测神经胶质瘤患者的五年总生存率。高危患者的多个复杂功能和分子信号通路发生改变,高低危患者的基因改变明显不同。我们还发现,高低危患者的不同生存结局可能与免疫过滤水平和肿瘤微环境的差异有关。随后,我们鉴定了几种可能有利于神经胶质瘤患者治疗的小分子化合物。最后,在神经胶质瘤和非肿瘤组织样本中验证了预后模型中 HDAC 基因的表达水平。我们的研究结果揭示了 HDAC 基因在神经胶质瘤中的临床应用价值和潜在分子机制。基于六个 HDAC 基因的模型可以很好地预测神经胶质瘤患者的总体生存率,这些基因是潜在的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e364/9134955/cc2edcd6fe5c/aging-14-204071-g001.jpg

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