Expression of HOXB2, a retinoic acid signaling target in pancreatic cancer and pancreatic intraepithelial neoplasia.

摘要: Purpose: Despite significant progress in understanding the molecular pathology of pancreatic cancer and its precursor lesion: intraepithelial neoplasia (PanIN), there remain no molecules with proven clinical utility as prognostic or therapeutic markers. Here, we used oligonucleotide microarrays to interrogate mRNA expression tissue normal pancreas identify novel pathways dysregulated development progression cancer. Experimental Design: RNA was hybridized Affymetrix Genechip HG-U133 microarrays. A relational database integrating data from publicly available resources created candidate genes potentially relevant The protein one candidate, homeobox B2 (HOXB2), PanIN assessed using immunohistochemistry. Results: We identified aberrant several components retinoic acid (RA) signaling pathway (RARα, MUC4, Id-1, MMP9, uPAR, HB-EGF, HOXB6, HOXB2), many which are known be aberrantly expressed PanIN. HOXB2, a downstream target RA, up-regulated 6.7-fold compared pancreas. Immunohistochemistry revealed ectopic HOXB2 15% early lesions 48 128 (38%) specimens. Expression associated nonresectable tumors an independent predictor poor survival resected tumors. Conclusions: RA cancer, including proportion lesions. Ectopic prognosis for all patients who underwent resection.