Exploring the Functional Disorder and Corresponding Key Transcription Factors in Intraductal Papillary Mucinous Neoplasms Progression.

Guiying Bai,Yingtang Gao,Chenxuan Wu,Guiming Shu

doi:10.1155/2015/197603

Abstract

This study has analyzed the gene expression patterns of an IPMN microarray dataset including normal pancreatic ductal tissue (NT), intraductal papillary mucinous adenoma (IPMA), intraductal papillary mucinous carcinoma (IPMC), and invasive ductal carcinoma (IDC) samples. And eight clusters of differentially expressed genes (DEGs) with similar expression pattern were detected by k-means clustering. Then a survey map of functional disorder in IPMN progression was established by functional enrichment analysis of these clusters. In addition, transcription factors (TFs) enrichment analysis was used to detect the key TFs in each cluster of DEGs, and three TFs (FLI1, ERG, and ESR1) were found to significantly regulate DEGs in cluster 1, and expression of these three TFs was validated by qRT-PCR. All these results indicated that these three TFs might play key roles in the early stages of IPMN progression.

Highlights

Intraductal papillary mucinous neoplasms (IPMN) are pancreatic precancerous lesions composed of dilated main and branch ducts and mixed duct type lined by mucin producing atypical epithelium, which usually proliferates in a papillary fashion [1]
To investigate the gene expression patterns in IPMN progression, multiclass significance analysis of microarrays (SAM) algorithm was used to screen the differentially expressed genes (DEGs) among four stages of carcinogenesis, and 2658 DEGs were identified
There were 88 DEGs that overlap with the known cancer genes, including pancreatic ductal adenocarcinoma (PDAC) related genes such as MYC, BRCA1, and KRAS [23,24,25], which indicates that the DEGs of this study have close bond with the cancer progression

Summary

Introduction

Intraductal papillary mucinous neoplasms (IPMN) are pancreatic precancerous lesions composed of dilated main and branch ducts and mixed duct type (main and branch ducts are both involved) lined by mucin producing atypical epithelium, which usually proliferates in a papillary fashion [1]. Based on their increasing architectural and nuclear atypia, IPMN are divided into four stages: IPMN low-grade dysplasia (alternatively intraductal papillary mucinous adenoma, IPMA), IPMN intermediate grade dysplasia (alternatively borderline IPMN, IPMB), and IPMN high-grade dysplasia (alternatively intraductal papillary mucinous carcinoma, IPMC) and about 20% to 40% IPMC were invasive ductal carcinoma (IDC) [1, 2]. The comprehensive integrated analysis of genes and biological processes and pathways leading to development and progression to malignancy of IPMN were still not clearly demonstrated

Methods

Results

Discussion

Conclusion