Wang Shanshan, Zou Xuan, Chen Yajie, Cho William C, Zhou Xiang
Cancer Institute, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China.
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Front Genet. 2021 Jan 28;11:580036. doi: 10.3389/fgene.2020.580036. eCollection 2020.
The N6-methyladenosine (mA) modification plays a critical role in cancer development. Little is known about the mA modification in triple-negative breast cancer (TNBC), the most aggressive subtype of breast cancer. Thus, the prognostic value of mA RNA methylation in TNBC deserves exploration. The expression levels of the 13 mA methylation regulators were compared between the 98 TNBC tumor samples and normal tissue samples based on the transcriptome profiles from The Cancer Genome Atlas (TCGA). The association between the mA regulators and patients' overall survival was assessed by Kaplan-Meier survival analysis and Cox regression analysis. Lasso regression analysis was conducted to construct a prognostic model based on the mA methylation system. The prognostic performance of the identified model was validated in GSE88847 and GSE135565 datasets. A nomogram combining the TNM stage and the mA prognostic model was further constructed for the survival prediction of TNBC patients. The mA regulator genes were remarkably dysregulated in TNBC tumor tissues, with , and significantly up-regulated and , and significantly down-regulated ( < 0.01). The expression level of was an independent unfavorable prognostic factor ( = 3.327, = 0.006), while ( = 0.425, = 0.009) was an independent favorable prognostic factor for TNBC patients. A prognostic model consisting of and was therefore proposed displaying higher accuracy of risk prediction when combined with TNM stage with an AUC of 0.791. The prognostic value of the identified signature remained consistent within the two external validation datasets. The mA methylation regulators were significantly dysregulated in TNBC tissues and could constitute a novel prognostic signature for the survival prediction of TNBC patients.
N6-甲基腺苷（m⁶A）修饰在癌症发展中起关键作用。对于三阴性乳腺癌（TNBC）这种最具侵袭性的乳腺癌亚型中的m⁶A修饰，人们了解甚少。因此，m⁶A RNA甲基化在TNBC中的预后价值值得探索。基于来自癌症基因组图谱（TCGA）的转录组谱，比较了98例TNBC肿瘤样本和正常组织样本中13种m⁶A甲基化调节因子的表达水平。通过Kaplan-Meier生存分析和Cox回归分析评估m⁶A调节因子与患者总生存期之间的关联。进行Lasso回归分析以构建基于m⁶A甲基化系统的预后模型。在GSE88847和GSE135565数据集中验证了所识别模型的预后性能。进一步构建了一个结合TNM分期和m⁶A预后模型的列线图，用于预测TNBC患者的生存情况。m⁶A调节因子基因在TNBC肿瘤组织中明显失调，其中[具体基因1] [具体基因2]和[具体基因3]显著上调，而[具体基因4] [具体基因5]和[具体基因6]显著下调（P < 0.01）。[具体基因7]的表达水平是一个独立的不良预后因素（HR = 3.327，P = 0.006），而[具体基因8]（HR = 0.425，P = 0.009）是TNBC患者的一个独立良好预后因素。因此，提出了一个由[具体基因7]和[具体基因8]组成的预后模型，当与TNM分期结合时，显示出更高的风险预测准确性，AUC为0.791。所识别特征的预后价值在两个外部验证数据集中保持一致。m⁶A甲基化调节因子在TNBC组织中显著失调，并可为TNBC患者的生存预测构成一种新的预后特征。
