Molecular Subtypes of Pancreatic Cancer Based on miRNA Expression Profiles Have Independent Prognostic Value

Abstract

Background and Aim Altered microRNAs (miRNA) expression, a typical feature of many cancers, is reportedly associated with prognosis according to several studies. Although numerous studies on miRNAs in pancreatic ductal adenocarcinoma have also attempted to identify prognostic biomarkers, more large-scale clinical studies are needed to establish the clinical significance of the results. Present study aimed to identify prognosis-related molecular subtypes of primary pancreas cancers using miRNA expression profiling. Methods Expression profiles of 1,733 miRNAs were obtained by using microarray analysis of 104 pancreatic tumors of Korean patients. To detect subgroups informative in predicting the patients prognosis, unsupervised clustering method was applied and then the association of the molecular subgroups with survival time was analyzed. Then, classifiers to predict the subgroup using penalized regression models were identified. Results Three PDAC tumor subtypes associated with prognosis based on miRNA expression profiles were determined. These subtypes showed significantly different survival time for patients with the same clinical conditions. This demonstrates that this prognostic molecular subgroup has independent prognostic utility. The molecular subtypes can be predicted with classifiers of 19 miRNAs. Of the 19 signature miRNAs, miR-106b-star, miR-324-3p, and mir-615 were related to a p53 canonical pathway, and miR-324, miR-145-5p, miR-26b-5p, and miR-574-3p were related to a Cox-2 centered pathway. Conclusions This study demonstrated that pancreatic cancers may be classified into molecular subtypes based on their miRNA profiles and could be used to predict prognosis. Several classifier miRNAs can discriminate these prognostic molecular subtypes. Further studies are needed for validation.