Fan Yuxiang, Peng Xinyu, Wang Yubo, Li Baoqin, Zhao Gang
Department of Neurosurgery, The First Hospital of Jilin University, Changchun, China.
Department of Hepatobiliary Pancreatic Surgery, The First Hospital of Jilin University, Changchun, China.
Front Mol Biosci. 2021 Sep 1;8:720020. doi: 10.3389/fmolb.2021.720020. eCollection 2021.
The histone deacetylase (HDAC) family limited accessibility to chromatin containing tumor suppressor genes by removing acetyl groups, which was deemed a path for tumorigenesis. Considering glioma remained one of the most common brain cancers with a dichotomy prognosis and limited therapy responses, HDAC inhibitors were an area of intensive research. However, the expression profiles and prognostic value of the HDACs required more elucidation. Multiple biomedical databases were incorporated, including ONCOMINE, GEPIA, TCGA, CGGA, GEO, TIMER, cBioPortal, and Metascape, to study expression profiles, prognostic value, immune infiltration, mutation status, and enrichment of HDACs in glioma. STRING and GeneMANIA databases were used to identify -related molecules. LASSO regression, Cox regression, Kaplan-Meier plot, and receiver operating characteristic (ROC) analyses were performed for -related signature construction and validation. was significantly overexpressed in glioma, while was downregulated in glioblastoma. Except for , the HDAC family expression was significantly associated with glioma grade. Most of the HDAC family also correlated with glioma genetic mutations. Higher expression level predicted more dismal overall survival (OS) ( < 0.0001) and disease-free survival (DFS) ( < 0.0001), but a higher level of held more favorable OS ( = 2.1e-14) and DFS ( = 4.8e-08). displayed the highest mutation ratio, at 2.6% of the family. The prognostic value of was validated with ROC achieving 0.70, 0.77, 0.75, and 0.80 as separability for 1-, 3-, 5-, and 10-years OS predictions in glioma, respectively. Moreover, expression positively correlated with neutrophil (r = 0.60, = 2.88e-47) and CD4 T cell infiltration (r = 0.52, = 3.96e-35) in lower-grade glioma. The final -related signature comprised of , (Hazard Ratio:1.49, 95%Confidence Interval:1.20-1.86), , , and , and was verified by survival analysis ( < 0.0001) and ROC with 0.80, 0.84, 0.83, and 0.88 as separability for 1-, 3-, 5-, and 10-years OS predictions, respectively. The signature was enriched in chromatin binding. HDAC family was of clinical significance for glioma. Most of the HDAC family significantly correlated with the glioma grade, mutation, and codeletion. was both a prognostic and immune infiltration indicator and a central component of the -related signature for precise prognosis prediction in glioma.
组蛋白去乙酰化酶（HDAC）家族通过去除乙酰基团限制了对含有肿瘤抑制基因的染色质的可及性，这被认为是肿瘤发生的一条途径。鉴于胶质瘤仍然是最常见的脑癌之一，其预后存在差异且治疗反应有限，HDAC抑制剂成为了一个深入研究的领域。然而，HDAC的表达谱和预后价值需要更多的阐释。纳入了多个生物医学数据库，包括ONCOMINE、GEPIA、TCGA、CGGA、GEO、TIMER、cBioPortal和Metascape，以研究HDAC在胶质瘤中的表达谱、预后价值、免疫浸润、突变状态和富集情况。使用STRING和GeneMANIA数据库来识别相关分子。进行LASSO回归、Cox回归、Kaplan-Meier曲线和受试者工作特征（ROC）分析以构建和验证相关特征。在胶质瘤中显著过表达，而在胶质母细胞瘤中下调。除了 ，HDAC家族的表达与胶质瘤分级显著相关。大多数HDAC家族也与胶质瘤基因突变相关。较高的 表达水平预示着更差的总生存期（OS）（ < 0.0001）和无病生存期（DFS）（ < 0.0001），但较高水平的 具有更有利的OS（ = 2.1e - 14）和DFS（ = 4.8e - 08）。 显示出最高的突变率，占该家族的2.6%。 的预后价值通过ROC验证，在胶质瘤1年、3年、5年和10年OS预测中的可分离性分别达到0.70、0.77、0.75和0.80。此外，在低级别胶质瘤中， 表达与中性粒细胞（r = 0.60， = 2.88e - 47）和CD4 T细胞浸润（r = 0.52， = 3.96e - 35）呈正相关。最终的相关特征由 、 （风险比：1.49，95%置信区间：1.20 - 1.86）、 、 和 组成，并通过生存分析（ < 0.0001）和ROC验证，在1年、3年、5年和10年OS预测中的可分离性分别为0.80、0.84、0.83和0.88。该特征在染色质结合中富集。HDAC家族对胶质瘤具有临床意义。大多数HDAC家族与胶质瘤分级、 突变和 共缺失显著相关。 既是预后和免疫浸润指标，也是胶质瘤精确预后预测的相关特征的核心组成部分。
