Chen Shuchen, Duan He, Xie Yusai, Li Xiaoling, Zhao Yuxia
Department of Radiation Oncology, The Fourth Affiliated Hospital of China Medical University, Shenyang, China.
Department of Thoracic Cancer 1, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, China.
Ann Transl Med. 2021 May;9(10):872. doi: 10.21037/atm-21-2113.
Rho GTPase-activating protein 11A (ARHGAP11A) is a member of the Rho GTPase-activating protein (RhoGAP) subfamily. However, its expression, prognostic significance and clinicopathologic factors correlation in lung adenocarcinoma is still unclear.
The original gene expression profile, survival data, and clinical information of patients with lung adenocarcinoma (LUAD) were downloaded from The Cancer Genome Atlas (TCGA) database. The expression difference of ARHGAP11A between LUAD tissues and adjacent normal tissues in the TCGA database was analyzed by using R software, and verified by the Oncomine database and immunohistochemical (IHC) assay of LUAD sections. Logistic regression was applied to analyze the relationship between the expression of ARHGAP11A and clinicopathological factors of LUAD. Kaplan-Meier (KM) survival curves and a Cox proportional-hazards model were selected to evaluate the prognostic significance of ARHGAP11A expression. Gene set enrichment analysis (GSEA) software was applied to screen the tumor signaling pathways associated with the low and high expression group of ARHGAP11A in LUAD.
The TCGA database showed that the expression of ARHGAP11A was significantly higher in LUAD tissues than in normal tissues (P<0.001). The up-regulation of ARHGAP11A in LUAD was verified by the Oncomine database (P<0.001) and IHC assay (P<0.001). Logistic regression analysis revealed the high expression of ARHGAP11A to be closely related to age, sex, advanced pathological stage, advanced T stage, and lymph node metastasis. The KM plots based on the TCGA and KM plotter databases indicated that patients with LUAD highly expressing ARHGAP11A had a poorer overall survival (OS) than patients with low expression of ARHGAP11A. Multivariate Cox regression analysis showed that the high expression of ARHGAP11A could be an important independent predictor of a poor prognosis of LUAD [hazards ratio (HR) =1.385; P<0.001]. GSEA indicated that 10 signal pathways were significantly enriched in LUAD samples with the ARHGAP11A expression phenotype.
ARHGAP11A may play a carcinogenic role in the malignant progression of LUAD, and it can be considered as a new independent prognostic factor and potential therapeutic target for LUAD.
Rho GTP酶激活蛋白11A(ARHGAP11A)是Rho GTP酶激活蛋白(RhoGAP)亚家族的成员。然而,其在肺腺癌中的表达、预后意义及与临床病理因素的相关性仍不清楚。
从癌症基因组图谱(TCGA)数据库下载肺腺癌(LUAD)患者的原始基因表达谱、生存数据和临床信息。使用R软件分析TCGA数据库中LUAD组织与相邻正常组织之间ARHGAP11A的表达差异,并通过Oncomine数据库和LUAD切片的免疫组织化学(IHC)检测进行验证。应用逻辑回归分析ARHGAP11A的表达与LUAD临床病理因素之间的关系。选择Kaplan-Meier(KM)生存曲线和Cox比例风险模型来评估ARHGAP11A表达的预后意义。应用基因集富集分析(GSEA)软件筛选与LUAD中ARHGAP11A低表达和高表达组相关的肿瘤信号通路。
TCGA数据库显示,LUAD组织中ARHGAP11A的表达明显高于正常组织(P<0.001)。Oncomine数据库(P<0.001)和IHC检测(P<0.001)验证了LUAD中ARHGAP11A的上调。逻辑回归分析显示,ARHGAP11A的高表达与年龄、性别、晚期病理分期、晚期T分期和淋巴结转移密切相关。基于TCGA和KM plotter数据库的KM图表明,ARHGAP11A高表达的LUAD患者的总生存期(OS)比ARHGAP11A低表达的患者差。多变量Cox回归分析表明,ARHGAP11A的高表达可能是LUAD预后不良的重要独立预测因素[风险比(HR)=1.385;P<0.001]。GSEA表明,10条信号通路在具有ARHGAP11A表达表型的LUAD样本中显著富集。
ARHGAP11A可能在LUAD的恶性进展中发挥致癌作用,可被视为LUAD的一个新的独立预后因素和潜在治疗靶点。