A novel methylation signature predicts inferior outcome of patients with PDAC

Abstract

Pancreatic ductal adenocarcinoma (PDAC) will become the second most common cause of death in North America and Europe over the next 10 years owing to the lack of early diagnosis, poor treatment, and poor prognosis. This study evaluated the methylation array data of 184 patients with PDAC in The Cancer Genome Atlas database to explore methylation biomarkers related to patient outcome. Using Univariable Cox regression analysis and Lasso regression analysis method in the training dataset, it was found that the four DNA methylation markers (CCNT1, ITGB3, SDS, and HMOX2) were significantly correlated with the overall survival of patients with PDAC. Kaplan-Meier analysis showed that these four DNA methylation markers could significantly distinguish high-risk and low-risk patients. Receiver operating characteristic analysis further confirmed that the four DNA methylation markers had high sensitivity and specificity, which could predict the prognosis of patients. Moreover, there was a difference in the genetic mutations between high-risk and low-risk patients distinguished by the four-DNA methylation model, which can provide information for clinical treatment. Finally, compared with known biomarkers, the model was more accurate in predicting the prognosis of PDAC. This four-DNA methylation model has potential as a new independent prognostic indicator, and could be used for the diagnosis, monitoring, and precision medicine of pancreatic cancer.