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.

Cell-Free DNA Methylation as Blood-Based Biomarkers for Pancreatic Adenocarcinoma—A Literature Update

“…These findings are consistent with a study of PDAC tissue [ 45 ] describing a methylation signature associated with short survival time and another methylation signature associated with long survival time. Likewise, Minqi Gu et al [ 46 ] identified a four-gene methylation signature ( CCNT1 , ITGB3 , SDS and HMOX2 ) in tumor tissue to predict the prognosis of PDAC patients. Based on the methylation signature patients were divided into a high-risk and a low-risk group [ 46 ].…”

“…Likewise, Minqi Gu et al [ 46 ] identified a four-gene methylation signature ( CCNT1 , ITGB3 , SDS and HMOX2 ) in tumor tissue to predict the prognosis of PDAC patients. Based on the methylation signature patients were divided into a high-risk and a low-risk group [ 46 ]. These results indicate that DNA hypermethylation has the potential to provide prognostic information in addition to the TNM classification, which clearly would benefit patients and clinicians’ therapeutic decisions and facilitate the correct choice of treatment.…”

Construction of immune related prognostic model for pancreatic ductal adenocarcinoma based on single cell RNA-seq analysis

“…Various diagnostic and prognostic models for PDAC based on genes expression and mutation have been proposed using bulk-seq datasets [13][14][15][16]. Nevertheless, the construction of prognostic model by integrating multiple scRNA-seq and bulk-seq datasets has not been reported.…”

Development and validation of prognostic and diagnostic model for pancreatic ductal adenocarcinoma based on scRNA-seq and bulk-seq datasets

“…The development of bioinformatics and multiomics database makes it easier to explore the expression pattern of malignancies and to construct prognostic and diagnostic models. Various risk score formulas have been proposed to predict the occurrence and prognosis of PDAC based on differential expression genes (DEGs) from bulk-seq datasets, such as The Cancer Genome Atlas (TCGA) or Gene Expression Omnibus (GEO) ( 9–12 ). However, bulk-seq only indicates average expression level of the whole tissue, which might lead to the bias for individual tumor cell.…”