PDF(Pubmed)
Abstract：
UNASSIGNED: Hepatocellular carcinoma (HCC) is one of the most common malignant tumours worldwide. Clarification of the somatic mutational landscape of important genes could reveal new therapeutic targets and facilitate individualized therapeutic approaches for HCC patients. The mutation and expression changes in the ARID1A gene in HCC remain controversial.
UNASSIGNED: First, cBioPortal was used to visualize genetic alterations and DNA copy number alterations (CNAs) in ARID1A. The relationships between ARID1A mutation status and HCC patient clinicopathological features and overall survival (OS) were also determined. Then, a meta-analysis was performed to evaluate the effect of ARID1A mutation or expression on the prognosis of HCC patients. Finally, the role of ARID1A in HCC progression was verified by in vitro experiments.
UNASSIGNED: ARID1A mutation was detected in 9.35% (33/353) of sequenced HCC cases, and ARID1A mutation decreased ARID1A mRNA expression. Patients with ARID1A alterations presented worse OS than those without ARID1A alterations. Meta-analysis and human HCC tissue microarray (TMA) analysis revealed that HCC patients with low ARID1A expression had worse OS and relapse-free survival (RFS), and low ARID1A expression was negatively correlated with tumour size. Then, ARID1A gain-of-function and loss-of-function experiments demonstrated the tumour suppressor role of ARID1A in HCC in vitro. In terms of the mechanism, we found that ARID1A could inhibit HCC progression by regulating retinoblastoma-like 1 (RBL1) expression via the JNK/FOXO3 pathway.
UNASSIGNED: ARID1A can be considered a potential prognostic biomarker and candidate therapeutic target for HCC.
UNASSIGNED: First, cBioPortal was used to visualize genetic alterations and DNA copy number alterations (CNAs) in ARID1A. The relationships between ARID1A mutation status and HCC patient clinicopathological features and overall survival (OS) were also determined. Then, a meta-analysis was performed to evaluate the effect of ARID1A mutation or expression on the prognosis of HCC patients. Finally, the role of ARID1A in HCC progression was verified by in vitro experiments.
UNASSIGNED: ARID1A mutation was detected in 9.35% (33/353) of sequenced HCC cases, and ARID1A mutation decreased ARID1A mRNA expression. Patients with ARID1A alterations presented worse OS than those without ARID1A alterations. Meta-analysis and human HCC tissue microarray (TMA) analysis revealed that HCC patients with low ARID1A expression had worse OS and relapse-free survival (RFS), and low ARID1A expression was negatively correlated with tumour size. Then, ARID1A gain-of-function and loss-of-function experiments demonstrated the tumour suppressor role of ARID1A in HCC in vitro. In terms of the mechanism, we found that ARID1A could inhibit HCC progression by regulating retinoblastoma-like 1 (RBL1) expression via the JNK/FOXO3 pathway.
UNASSIGNED: ARID1A can be considered a potential prognostic biomarker and candidate therapeutic target for HCC.
摘要：
■肝细胞癌（HCC）是全球最常见的恶性肿瘤之一。阐明重要基因的体细胞突变景观可以揭示新的治疗靶标，并促进HCC患者的个性化治疗方法。HCC中ARID1A基因的突变和表达变化仍存在争议。
■首先，cBioPortal用于可视化ARID1A中的遗传改变和DNA拷贝数改变(CNAs)。还确定了ARID1A突变状态与HCC患者临床病理特征和总生存期（OS）之间的关系。然后，进行了一项荟萃分析,以评估ARID1A突变或表达对HCC患者预后的影响.最后,通过体外实验验证了ARID1A在HCC进展中的作用.
■在9.35%（33/353）的肝癌测序病例中检测到ARID1A突变，ARID1A突变降低ARID1AmRNA表达。有ARID1A改变的患者的OS比没有ARID1A改变的患者差。Meta分析和人肝癌组织芯片（TMA）分析显示，低ARID1A表达的肝癌患者OS和无复发生存期（RFS）较差，低ARID1A表达与肿瘤大小呈负相关。然后，ARID1A功能获得和功能丧失实验证明了ARID1A在体外肝癌中的肿瘤抑制作用。在机制方面,我们发现ARID1A可以通过JNK/FOXO3通路调节视网膜母细胞瘤样1(RBL1)的表达,从而抑制HCC的进展.
■ARID1A可被认为是HCC的潜在预后生物标志物和候选治疗靶点。
■首先，cBioPortal用于可视化ARID1A中的遗传改变和DNA拷贝数改变(CNAs)。还确定了ARID1A突变状态与HCC患者临床病理特征和总生存期（OS）之间的关系。然后，进行了一项荟萃分析,以评估ARID1A突变或表达对HCC患者预后的影响.最后,通过体外实验验证了ARID1A在HCC进展中的作用.
■在9.35%（33/353）的肝癌测序病例中检测到ARID1A突变，ARID1A突变降低ARID1AmRNA表达。有ARID1A改变的患者的OS比没有ARID1A改变的患者差。Meta分析和人肝癌组织芯片（TMA）分析显示，低ARID1A表达的肝癌患者OS和无复发生存期（RFS）较差，低ARID1A表达与肿瘤大小呈负相关。然后，ARID1A功能获得和功能丧失实验证明了ARID1A在体外肝癌中的肿瘤抑制作用。在机制方面,我们发现ARID1A可以通过JNK/FOXO3通路调节视网膜母细胞瘤样1(RBL1)的表达,从而抑制HCC的进展.
■ARID1A可被认为是HCC的潜在预后生物标志物和候选治疗靶点。
