Li Jianhao, Rao Benchen, Yang Jie, Liu Liwen, Huang Maoxin, Liu Xin, Cui Guangying, Li Chao, Han Qicai, Yang Hao, Cui Xichun, Sun Ranran
Precision Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Key Laboratory of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Front Oncol. 2020 Jun 2;10:769. doi: 10.3389/fonc.2020.00769. eCollection 2020.
Osteosarcoma (OS) is the most common primary bone tumor. The disease has a poor prognosis due to the delay in the diagnosis and the development of metastasis. N6-Methyladenosine (m6A)-related regulators play an essential role in various tumors. In this study, a comprehensive analysis was conducted to elucidate the relationship between the expression profiles of m6A-related molecules and the clinical outcome of OS patients. Public genome datasets and a tissue microarray (TMA) cohort were used to analyze the mRNA and protein expression levels of m6A regulators. Next, immunofluorescence (IF) analysis was used to determine the subcellular localization of m6A-related molecules. Kaplan-Meier and Cox regression analyses were performed to confirm the prognostic value of m6A-related molecules in OS. A comprehensive bioinformatic analysis was conducted to identify the potential molecular mechanisms mediated by m6A modification in OS. We found that m6A-related regulator expression was dysregulated in OS tissues, especially in metastatic tumor tissues. Low expression of METTL3, METTL14, and YTHDF2 and high expression of KIAA1429 and HNRNPA2B1 were significantly associated with poor prognosis in the TMA cohort. Simultaneously, the genome meta-cohort analysis revealed that low expression of FTO and METTL14 and high expression of METTL3, HNRNPA2B1, and YTHDF3 were associated with poor prognosis in OS. Cox regression analysis showed that HNRNPA2B1 might be an independent risk factor for OS. Bioinformatic analysis indicated that m6A regulators might be involved in OS progression through humoral immune response and cell cycle pathways. M6A-related regulators are frequently dysregulated and correlate with metastasis and prognosis in OS. M6A-related regulators may serve as novel therapeutic targets and prognostic biomarkers for OS.
骨肉瘤（OS）是最常见的原发性骨肿瘤。由于诊断延迟和转移的发生，该疾病预后较差。N6-甲基腺苷（m6A）相关调节因子在各种肿瘤中发挥着重要作用。在本研究中，进行了一项综合分析，以阐明m6A相关分子的表达谱与OS患者临床结局之间的关系。使用公共基因组数据集和组织微阵列（TMA）队列来分析m6A调节因子的mRNA和蛋白质表达水平。接下来，采用免疫荧光（IF）分析来确定m6A相关分子的亚细胞定位。进行Kaplan-Meier和Cox回归分析以确认m6A相关分子在OS中的预后价值。进行了全面的生物信息学分析，以确定OS中m6A修饰介导的潜在分子机制。我们发现，m6A相关调节因子的表达在OS组织中失调，尤其是在转移性肿瘤组织中。在TMA队列中，METTL3、METTL14和YTHDF2的低表达以及KIAA1429和HNRNPA2B1的高表达与不良预后显著相关。同时，基因组meta队列分析显示，FTO和METTL14的低表达以及METTL3、HNRNPA2B1和YTHDF3的高表达与OS的不良预后相关。Cox回归分析表明，HNRNPA2B1可能是OS的独立危险因素。生物信息学分析表明，m6A调节因子可能通过体液免疫反应和细胞周期途径参与OS进展。m6A相关调节因子经常失调，并与OS的转移和预后相关。m6A相关调节因子可能作为OS的新型治疗靶点和预后生物标志物。
