Oligonucleotide microarray identifies genes differentially expressed during tumorigenesis of DMBA-induced pancreatic cancer in rats

• Published in: PloS one Vol. 8; no. 12; p. e82910
• Main Authors: Guo, Jun-Chao, Li, Jian, Yang, Ying-Chi, Zhou, Li, Zhang, Tai-Ping, Zhao, Yu-Pei
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 23.12.2013; Public Library of Science (PLoS)
• Subjects: 9,10-Dimethyl-1,2-benzanthracene; Animals; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Cancer; Cancer genetics; Carcinogenesis; Carcinogenesis - genetics; Carcinogenesis - metabolism; Carcinogenesis - pathology; Carcinogens; Cell Line, Tumor; Chemokines; Cluster analysis; Clustering; DNA microarrays; Gene expression; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Genes; Homology; Humans; Immunohistochemistry; Male; Medical prognosis; Metastasis; Molecular Sequence Annotation; Mutation; Oligonucleotide Array Sequence Analysis; Oligonucleotides; Pancreas; Pancreas - metabolism; Pancreas - pathology; Pancreatic cancer; Pancreatic Neoplasms; Pancreatic Neoplasms - chemically induced; Pancreatic Neoplasms - genetics; Pancreatic Neoplasms - metabolism; Pancreatic Neoplasms - pathology; Pancreatitis; Pancreatitis, Acute Necrotizing - chemically induced; Pancreatitis, Acute Necrotizing - genetics; Pancreatitis, Acute Necrotizing - metabolism; Pancreatitis, Acute Necrotizing - pathology; Pancreatitis, Chronic - chemically induced; Pancreatitis, Chronic - genetics; Pancreatitis, Chronic - metabolism; Pancreatitis, Chronic - pathology; Polymerase chain reaction; Prognosis; Rats; Rats, Sprague-Dawley; Receptors, CXCR - genetics; Receptors, CXCR - metabolism; Rodents; Studies; Surgery; Tumorigenesis; Ubiquitin-Conjugating Enzymes - genetics; Ubiquitin-Conjugating Enzymes - metabolism; Beijing China; China
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0082910

The extremely dismal prognosis of pancreatic cancer (PC) is attributed, at least in part, to lack of early diagnosis. Therefore, identifying differentially expressed genes in multiple steps of tumorigenesis of PC is of great interest. In the present study, a 7,12-dimethylbenzanthraene (DMBA)-induced PC model was established in male Sprague-Dawley rats. The gene expression profile was screened using an oligonucleotide microarray, followed by real-time quantitative polymerase chain reaction (qRT-PCR) and immunohistochemical staining validation. A total of 661 differentially expressed genes were identified in stages of pancreatic carcinogenesis. According to GO classification, these genes were involved in multiple molecular pathways. Using two-way hierarchical clustering analysis, normal pancreas, acute and chronic pancreatitis, PanIN, early and advanced pancreatic cancer were completely discriminated. Furthermore, 11 upregulated and 142 downregulated genes (probes) were found by Mann-Kendall trend Monotone test, indicating homologous genes of rat and human. The qRT-PCR and immunohistochemistry analysis of CXCR7 and UBe2c, two of the identified genes, confirmed the microarray results. In human PC cell lines, knockdown of CXCR7 resulted in decreased migration and invasion. Collectively, our data identified several promising markers and therapeutic targets of PC based on a comprehensive screening and systemic validation.