Xiao He, He Weixiang, Chen Ping, Xu Deqiang, Zeng Guang, Li Zhuo, Huang Mingliu, Wang Xinghuan, DiSanto Michael E, Zhang Xinhua
Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, China.
Department of Urology, Shenzhen Sixth People's Hospital, Shenzhen, China.
Front Endocrinol (Lausanne). 2019 Jul 12;10:472. doi: 10.3389/fendo.2019.00472. eCollection 2019.
Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with an unfavorable prognosis and limited treatment options. Nevertheless, no clinically applicable molecular markers have been identified for the progression of ACCs. DNA methylation alterations were found to contribute to the development of ACC in recent decades. The aims of the current study was to identify the abnormally methylated differentially expressed genes (DEGs) in ACCs, and to elucidate the mechanistic basis for these changes. Analyses were conducted on gene expression and gene methylation profile datasets to identify the aberrantly methylated DEGs. The DAVID software was used to conduct the analyses of functional enrichment on screened genes. Finally, expression was validated, and the relationship between abnormally methylated DEGs and clinical features was determined via the Oncomine database and The Cancer Genome Atlas (TCGA). To further verify the altered expression and methylation status of our identified genes we also validated these changes at the tissue and cellular levels. We screened and identified 92 differentially expressed genes and 802 abnormally methylated genes. Furthermore, seven aberrantly methylated and dysregulated genes were identified and validated, along with a number of functional enriched pathways. Among these seven genes, the expression or methylation status is significantly correlated with different pathological stages and overall rates of survival. In validation, the expression of seven genes were significantly altered and five genes were hypermethylated in ACC. Our study identified abnormally methylated DEGs and potentially affected pathways in ACCs, from which we could begin to understand the basic molecular mechanisms of these alterations. Moreover, these abnormally methylated genes might serve as therapeutic targets and biomarkers to allow ACC patients to be more precisely diagnosed and effectively treated.
肾上腺皮质癌（ACC）是一种罕见的内分泌恶性肿瘤，预后不良且治疗选择有限。然而，尚未发现适用于临床的ACC进展分子标志物。近几十年来，发现DNA甲基化改变与ACC的发生发展有关。本研究的目的是识别ACC中异常甲基化的差异表达基因（DEG），并阐明这些变化的机制基础。对基因表达和基因甲基化谱数据集进行分析，以识别异常甲基化的DEG。使用DAVID软件对筛选出的基因进行功能富集分析。最后，通过Oncomine数据库和癌症基因组图谱（TCGA）验证基因表达，并确定异常甲基化的DEG与临床特征之间的关系。为了进一步验证我们所识别基因的表达和甲基化状态的改变，我们还在组织和细胞水平上验证了这些变化。我们筛选并识别出92个差异表达基因和802个异常甲基化基因。此外，还识别并验证了7个异常甲基化和失调的基因，以及一些功能富集的通路。在这7个基因中，其表达或甲基化状态与不同的病理阶段和总生存率显著相关。在验证过程中，ACC中7个基因的表达显著改变，5个基因发生高甲基化。我们的研究识别出了ACC中异常甲基化的DEG以及可能受影响的通路，从中我们可以开始了解这些改变的基本分子机制。此外，这些异常甲基化基因可能作为治疗靶点和生物标志物，使ACC患者能够得到更精确的诊断和有效治疗。
