Transcriptome analysis of microdissected pancreatic intraepithelial neoplastic lesions

被引:165
作者
Buchholz, M
Braun, M
Heidenblut, A
Kestler, HA
Klöppel, G
Schmiegel, W
Hahn, SA
Lüttges, J
Gress, TM
机构
[1] Univ Hosp Ulm, Dept Internal Med 1, D-89081 Ulm, Germany
[2] Ruhr Univ Bochum, Dept Internal Med, D-4630 Bochum, Germany
[3] Univ Kiel, Dept Pathol, D-2300 Kiel, Germany
关键词
PanIN progression; gene expression; early diagnosis; target genes;
D O I
10.1038/sj.onc.1208804
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Pancreatic ductal adenocarcinoma (PDAC) carries the most dismal prognosis of all solid tumours. Both the late clinical presentation of patients, due to lack of early symptoms, as well as the rapid and aggressive course of the disease contribute to the extremely high mortality of this malignancy. Recently, a multistep progression model for PDAC integrating morphological, clinical and molecular evidence has been proposed. Putative precursor lesions, termed pancreatic intraepithelial neoplasia (PanIN), are classified into three different grades (PanIN-1 through -3) based on the degree of cellular atypia they display. We have conducted large-scale expression pro. ling analyses of microdissected cells from normal pancreatic ducts, PanINs of different grades and PDACs using whole-genome oligonucleotide microarrays. Veri. cation of hybridisation results for selected genes was performed using quantitative real-time PCR and immunohistochemical analyses on PanIN tissue microarrays. Comparison of the expression profiles demonstrated that the greatest changes in gene expression occur between PanIN stages 1B and 2, suggesting that PanIN-2 may represent the first truly preneoplastic stage in PDAC progression. Our results identify a large number of potential target genes for the development of novel molecular diagnostic and therapeutic tools for the prevention and early diagnosis of PDAC and provide novel insights into the pathophysiological mechanisms involved in tumour progression in the pancreas.
引用
收藏
页码:6626 / 6636
页数:11
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