Comprehensive Analysis of HDAC Family Identifies HDAC1 as a Prognostic and Immune Infiltration Indicator and HDAC1-Related Signature for Prognosis in Glioma.
Comprehensive Analysis of HDAC Family Identifies HDAC1 as a Prognostic and Immune Infiltration Indicator and HDAC1-Related Signature for Prognosis in Glioma.
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HDAC 家族的综合分析确定 HDAC1 作为胶质瘤预后和免疫浸润指标以及与 HDAC1 相关的预后特征
DOI：
10.3389/fmolb.2021.720020
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发表时间：
2021
影响因子：
5
通讯作者：
Zhao G
中科院分区：
文献类型：
--
作者：
Fan Y;Peng X;Wang Y;Li B;Zhao G
背景：组蛋白脱乙酰酶(HDAC)家族通过去除乙酰基来限制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。考虑到胶质瘤仍然是最常见的脑癌之一，预后一分为二，治疗反应有限，HDAC抑制剂是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明。方法：利用Oncomine、GEPIA、TCGA、CGGA、GEO、Timer、cBioPortalTM和Metascape等生物医学数据库，研究HDACs在胶质瘤中的表达谱、预后价值、免疫浸润、突变状态和HDACs的富集性。用STRING和GeneMANIA数据库鉴定HDAC1相关分子。使用套索回归、Cox回归、Kaplan-Meier图和受试者操作特征(ROC)分析来构建和验证与HDAC1相关的签名。结果：HDAC1在胶质瘤中呈高表达，而HDAC11在胶质母细胞瘤中表达下调。除HDAC6/9/10外，HDAC家族的表达与胶质瘤分级显著相关。HDAC家族的大多数成员也与胶质瘤基因突变有关。HDAC1表达水平越高，总生存期(OS)(p&t；0.0001)和无病生存期(DFS)越差(p<；0.0001)，而HDAC11表达水平越高，OS(p=2.1E−14)和DFS(p=4.8E−08)越有利。HDAC4的突变率最高，为2.6%。在胶质瘤中，HDAC1的预后价值得到验证，ROC分别为0.70、0.77、0.75和0.80作为1、3、5和10年OS预测的可分离性。在低级别胶质瘤中，HDAC1表达与中性粒细胞(r=0.60，p=2.88e-47)和CD4+T细胞浸润(r=0.52，p=3.96e-35)呈正相关。最终的HDAC1相关签名由FKBP3、HDAC1(危险比：1.49，95%可信区间：1.20-1.86)、PHF21A、Runx1T1和RBL1组成，并通过生存分析(p<；0.0001)和ROC进行验证，1、3、5和10年OS预测的可分离性分别为0.80、0.84、0.83和0.88。该标记富含染色质结合。结论：HDAC家族对脑胶质瘤具有临床意义。大多数HDAC家族与胶质瘤分级、IDH1突变和1p/19q共缺失显著相关。HDAC1既是预后和免疫渗透指标，也是HDAC1相关信号的中心成分，可用于准确预测胶质瘤的预后。
Background: 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. Methods: 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 HDAC1-related molecules. LASSO regression, Cox regression, Kaplan-Meier plot, and receiver operating characteristic (ROC) analyses were performed for HDAC1-related signature construction and validation. Results: HDAC1 was significantly overexpressed in glioma, while HDAC11 was downregulated in glioblastoma. Except for HDAC 6/9/10, the HDAC family expression was significantly associated with glioma grade. Most of the HDAC family also correlated with glioma genetic mutations. Higher HDAC1 expression level predicted more dismal overall survival (OS) (p < 0.0001) and disease-free survival (DFS) (p < 0.0001), but a higher level of HDAC11 held more favorable OS (p = 2.1e−14) and DFS (p = 4.8e−08). HDAC4 displayed the highest mutation ratio, at 2.6% of the family. The prognostic value of HDAC1 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, HDAC1 expression positively correlated with neutrophil (r = 0.60, p = 2.88e-47) and CD4+ T cell infiltration (r = 0.52, p = 3.96e-35) in lower-grade glioma. The final HDAC1-related signature comprised of FKBP3, HDAC1 (Hazard Ratio:1.49, 95%Confidence Interval:1.20–1.86), PHF21A, RUNX1T1, and RBL1, and was verified by survival analysis (p < 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. Conclusion: HDAC family was of clinical significance for glioma. Most of the HDAC family significantly correlated with the glioma grade, IDH1 mutation, and 1p/19q codeletion. HDAC1 was both a prognostic and immune infiltration indicator and a central component of the HDAC1-related signature for precise prognosis prediction in glioma.
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影响因子：
7.3
作者：
Gao J;Aksoy BA;Dogrusoz U;Dresdner G;Gross B;Sumer SO;Sun Y;Jacobsen A;Sinha R;Larsson E;Cerami E;Sander C;Schultz N
通讯作者：
Schultz N
星形胶质瘤和正常脑组织中的12个组蛋白脱乙酰基酶（HDAC）基因的差异表达：II和IV类在胶质母细胞瘤中不表达。
影响因子：
3.8
作者：
Lucio-Eterovic AK;Cortez MA;Valera ET;Motta FJ;Queiroz RG;Machado HR;Carlotti CG Jr;Neder L;Scrideli CA;Tone LG
通讯作者：
Tone LG
GEPIA：用于癌症和正常基因表达谱和交互式分析的网络服务器。
影响因子：
14.9
作者：
Tang Z;Li C;Kang B;Gao G;Li C;Zhang Z
通讯作者：
Zhang Z
影响因子：
14.9
作者：
Colaprico A;Silva TC;Olsen C;Garofano L;Cava C;Garolini D;Sabedot TS;Malta TM;Pagnotta SM;Castiglioni I;Ceccarelli M;Bontempi G;Noushmehr H
通讯作者：
Noushmehr H
影响因子：
15.9
作者：
Trang Thi Thu Nguyen;Zhang, Yiru;Siegelin, Markus D.
通讯作者：
Siegelin, Markus D.