m⁶ A RNA methylation regulators contribute to malignant progression in rectal cancer

N6,2'-O-dimethyladenosine (m⁶ A) RNA methylation, which is correlated with cancer initiation and progression, is dynamically regulated by m⁶ 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 m⁶ 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 m⁶ 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, m⁶ A RNA methylation regulators can be regarded as potentially useful biomarkers for predicting the prognosis and designing a treatment strategy in rectal cancer.