Department of Gastrointestinal Surgery 2 Section, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.
J Cell Physiol. 2020 Sep;235(9):6300-6306. doi: 10.1002/jcp.29626. Epub 2020 Feb 11.
N6,2'-O-dimethyladenosine (m A) RNA methylation, which is correlated with cancer initiation and progression, is dynamically regulated by m A RNA methylation regulators, including writers, erasers, and readers. Two subgroups of rectal cancer, including cluster1 and cluster2, were identified based on consensus clustering to m A RNA methylation regulators. A protein-protein interaction network was constructed and hub genes were identified. The results demonstrated that the expression of WTAP was significantly associated with YTHDC1 and YTHDF2. The principal component analysis was used to compare the transcriptional profile between cluster1 and cluster2 subgroups. By using two identified m A RNA methylation regulators, we constructed a risk signature to predict the survival outcomes of rectal cancer. The results revealed that YTHDC2 and YTHDF2 were protective genes with HR < 1. The coefficients obtained from the least absolute shrinkage and selection operator algorithm were used to calculate the risk score. Patients were then divided into low- and high-risk groups based on the median risk score. The survival analysis demonstrated that there were significant differences in overall survival between these two groups (p < .05). The results of the univariate analysis showed that the risk score, AJCC stage, M stage, and age were associated with overall survival. The results of the multivariate Cox regression analysis showed that the risk score and age were still significantly associated with the overall survival (p < .05). To conclude, m A RNA methylation regulators can be regarded as potentially useful biomarkers for predicting the prognosis and designing a treatment strategy in rectal cancer.
N6,2'-O-二甲基腺苷(m A)RNA 甲基化与癌症的发生和发展相关,受 m A RNA 甲基化调控因子(包括写入器、擦除器和读取器)的动态调控。基于共识聚类,确定了两种直肠癌亚群,包括 cluster1 和 cluster2。构建了蛋白质-蛋白质相互作用网络,并鉴定了枢纽基因。结果表明,WTAP 的表达与 YTHDC1 和 YTHDF2 显著相关。主成分分析用于比较 cluster1 和 cluster2 亚群之间的转录谱。通过使用两个鉴定出的 m A RNA 甲基化调控因子,我们构建了一个风险签名来预测直肠癌的生存结局。结果表明,YTHDC2 和 YTHDF2 是 HR<1 的保护性基因。最小绝对收缩和选择算子算法获得的系数用于计算风险评分。然后根据中位数风险评分将患者分为低风险组和高风险组。生存分析表明,两组之间的总体生存率存在显著差异(p<.05)。单因素分析结果表明,风险评分、AJCC 分期、M 分期和年龄与总生存率相关。多因素 Cox 回归分析结果表明,风险评分和年龄与总生存率仍显著相关(p<.05)。总之,m A RNA 甲基化调控因子可作为预测直肠癌预后和制定治疗策略的潜在有用生物标志物。