Department of Oncology, Third Xiangya Hospital, Central South University, Changsha, China.
Department of Radiation Oncology, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China.
Front Immunol. 2021 Mar 3;12:637933. doi: 10.3389/fimmu.2021.637933. eCollection 2021.
Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with a high rate of mortality and recurrence. N6-methyladenosine methylation (m6A) is the most common modification to affect cancer development, but to date, the potential role of m6A regulators in ACC prognosis is not well understood. In this study, we systematically analyzed 21 m6A regulators in ACC samples from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) database. We identified three m6A modification patterns with different clinical outcomes and discovered a significant relationship between diverse m6A clusters and the tumor immune microenvironment (immune cell types and ESTIMATE algorithm). Additionally, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) revealed that the m6A clusters were strongly associated with immune infiltration in the ACC. Next, to further explore the m6A prognostic signatures in ACC, we implemented Lasso (Least Absolute Shrinkage and Selection Operator) Cox regression to establish an eight-m6A-regulator prognostic model in the TCGA dataset, and the results showed that the model-based high-risk group was closely correlated with poor overall survival (OS) compared with the low-risk group. Subsequently, we validated the key modifications in the GEO datasets and found that high HNRNPA2B1 expression resulted in poor OS and event-free survival (EFS) in ACC. Moreover, to further decipher the molecular mechanisms, we constructed a competing endogenous RNA (ceRNA) network based on HNRNPA2B1, which consists of 12 long noncoding RNAs (lncRNAs) and 1 microRNA (miRNA). In conclusion, our findings indicate the potential role of m6A modification in ACC, providing novel insights into ACC prognosis and guiding effective immunotherapy.
肾上腺皮质癌 (ACC) 是一种罕见的内分泌恶性肿瘤,死亡率和复发率都很高。N6-甲基腺苷修饰 (m6A) 是最常见的影响癌症发展的修饰,但迄今为止,m6A 调节剂在 ACC 预后中的潜在作用尚不清楚。在这项研究中,我们系统地分析了来自癌症基因组图谱 (TCGA) 和基因表达综合 (GEO) 数据库的 21 个 m6A 调节剂在 ACC 样本中的作用。我们发现了三种具有不同临床结局的 m6A 修饰模式,并发现了不同的 m6A 聚类与肿瘤免疫微环境(免疫细胞类型和 ESTIMATE 算法)之间的显著关系。此外,基因本体论 (GO)、京都基因与基因组百科全书 (KEGG) 和基因集富集分析 (GSEA) 表明,m6A 聚类与 ACC 中的免疫浸润密切相关。接下来,为了进一步探索 ACC 中的 m6A 预后特征,我们在 TCGA 数据集上实施了 Lasso (Least Absolute Shrinkage and Selection Operator) Cox 回归来建立一个 8-m6A-调节剂预后模型,结果表明该模型高风险组与低风险组相比,与不良总生存 (OS) 密切相关。随后,我们在 GEO 数据集上验证了关键修饰,并发现 HNRNPA2B1 高表达导致 ACC 中不良的 OS 和无事件生存 (EFS)。此外,为了进一步阐明分子机制,我们基于 HNRNPA2B1 构建了一个竞争内源性 RNA (ceRNA) 网络,该网络由 12 个长非编码 RNA (lncRNA) 和 1 个 microRNA (miRNA) 组成。总之,我们的研究结果表明 m6A 修饰在 ACC 中的潜在作用,为 ACC 的预后提供了新的见解,并指导有效的免疫治疗。
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