PDF(Pubmed)
Abstract：
BACKGROUND: Glioblastoma (GBM) is a high-grade and heterogeneous subtype of glioma that presents a substantial challenge to human health, characterized by a poor prognosis and low survival rates. Despite its known involvement in regulating leukemia and melanoma, the function and mechanism of DNAJC1 in GBM remain poorly understood.
METHODS: Utilizing data from the TCGA, CGGA, and GEO databases, we investigated the expression pattern of DNAJC1 and its correlation with clinical characteristics in GBM specimens. Loss-of-function experiments were conducted to explore the impact of DNAJC1 on GBM cell lines, with co-culture experiments assessing macrophage infiltration and functional marker expression.
RESULTS: Our analysis demonstrated frequent overexpression of DNAJC1 in GBM, significantly associated with various clinical characteristics including WHO grade, IDH status, chromosome 1p/19q codeletion, and histological type. Moreover, Kaplan‒Meier and ROC analyses revealed DNAJC1 as a negative prognostic predictor and a promising diagnostic biomarker for GBM patients. Functional studies indicated that silencing DNAJC1 impeded cell proliferation and migration, induced cell cycle arrest, and enhanced apoptosis. Mechanistically, DNAJC1 was implicated in stimulating extracellular matrix reorganization, triggering the epithelial-mesenchymal transition (EMT) process, and initiating immunosuppressive macrophage infiltration.
CONCLUSIONS: Our findings underscore the pivotal role of DNAJC1 in GBM pathogenesis, suggesting its potential as a diagnostic and therapeutic target for this challenging disease.
METHODS: Utilizing data from the TCGA, CGGA, and GEO databases, we investigated the expression pattern of DNAJC1 and its correlation with clinical characteristics in GBM specimens. Loss-of-function experiments were conducted to explore the impact of DNAJC1 on GBM cell lines, with co-culture experiments assessing macrophage infiltration and functional marker expression.
RESULTS: Our analysis demonstrated frequent overexpression of DNAJC1 in GBM, significantly associated with various clinical characteristics including WHO grade, IDH status, chromosome 1p/19q codeletion, and histological type. Moreover, Kaplan‒Meier and ROC analyses revealed DNAJC1 as a negative prognostic predictor and a promising diagnostic biomarker for GBM patients. Functional studies indicated that silencing DNAJC1 impeded cell proliferation and migration, induced cell cycle arrest, and enhanced apoptosis. Mechanistically, DNAJC1 was implicated in stimulating extracellular matrix reorganization, triggering the epithelial-mesenchymal transition (EMT) process, and initiating immunosuppressive macrophage infiltration.
CONCLUSIONS: Our findings underscore the pivotal role of DNAJC1 in GBM pathogenesis, suggesting its potential as a diagnostic and therapeutic target for this challenging disease.
摘要：
背景：胶质母细胞瘤（GBM）是一种高级别和异质亚型的神经胶质瘤，对人类健康构成重大挑战，预后差，生存率低。尽管已知它参与调节白血病和黑色素瘤，DNAJC1在GBM中的功能和机制仍然知之甚少。
方法：利用来自TCGA的数据，CGGA,和GEO数据库，我们研究了DNAJC1在GBM标本中的表达模式及其与临床特征的相关性。进行了功能丧失实验，以探讨DNAJC1对GBM细胞系的影响，与共培养实验评估巨噬细胞浸润和功能标记表达。
结果：我们的分析表明DNAJC1在GBM中频繁过表达，与各种临床特征显着相关，包括WHO等级，IDH状态,染色体1p/19q共缺失，和组织学类型。此外，Kaplan-Meier和ROC分析显示DNAJC1是GBM患者的阴性预后预测因子和有希望的诊断生物标志物。功能研究表明，沉默DNAJC1阻碍细胞增殖和迁移，诱导细胞周期停滞，并增强细胞凋亡。机械上,DNAJC1与刺激细胞外基质重组有关，触发上皮-间质转化（EMT）过程，并启动免疫抑制性巨噬细胞浸润。
结论：我们的发现强调了DNAJC1在GBM发病机制中的关键作用，提示其作为这种具有挑战性的疾病的诊断和治疗靶点的潜力。
方法：利用来自TCGA的数据，CGGA,和GEO数据库，我们研究了DNAJC1在GBM标本中的表达模式及其与临床特征的相关性。进行了功能丧失实验，以探讨DNAJC1对GBM细胞系的影响，与共培养实验评估巨噬细胞浸润和功能标记表达。
结果：我们的分析表明DNAJC1在GBM中频繁过表达，与各种临床特征显着相关，包括WHO等级，IDH状态,染色体1p/19q共缺失，和组织学类型。此外，Kaplan-Meier和ROC分析显示DNAJC1是GBM患者的阴性预后预测因子和有希望的诊断生物标志物。功能研究表明，沉默DNAJC1阻碍细胞增殖和迁移，诱导细胞周期停滞，并增强细胞凋亡。机械上,DNAJC1与刺激细胞外基质重组有关，触发上皮-间质转化（EMT）过程，并启动免疫抑制性巨噬细胞浸润。
结论：我们的发现强调了DNAJC1在GBM发病机制中的关键作用，提示其作为这种具有挑战性的疾病的诊断和治疗靶点的潜力。
