title: Gene expression abnormalities in histologically normal breast epithelium from patients with luminal type of breast cancer.
abstract: The gene expression profile of breast cancer has been described as a great breakthrough on the way to comprehend differences in cancer origin, behavior and therapy. However, gene expression profile in histologically normal epithelium (HNEpi) which could harbor genetic abnormalities predisposing breast tissue to develop malignancy was minor scope for scientists in the past. Thus, we aimed to analyze gene expressions in HNEpi and breast cancer tissue (BCTis) in order to establish its value as potential diagnostic marker for cancer development. We evaluated a panel of disease-specific genes in luminal type (A/B) of breast cancer and tumor surrounding HNEpi by qRT-PCR Array in 32 microdissected samples. There was 20.2 and 2.4% deregulation rate in genes with at least 2-fold or 5-fold over-expression between luminal (A/B) type breast carcinomas and tumor surrounding HNEpi, respectively. The high-grade luminal carcinomas showed higher number of deregulated genes compared to low-grade cases (50.6 vs. 23.8% with at least 2-fold deregulation rate). The main overexpressed genes in HNEpi were KLK5, SCGB1D2, GSN, EGFR and NGFR. The significant differences in gene expression between BCTis and HNEpi samples were revealed for BAG1, C3, CCNA2, CD44, FGF1, FOSL1, ID2, IL6R, NGFB, NGFR, PAPPA, PLAU, SERPINB5, THBS1 and TP53 gene (p < 0.05) and BCL2L2, CTSB, ITGB4, JUN, KIT, KLF5, SCGB1D2, SCGB2A1, SERPINE1 (p < 0.01), and EGFR, GABRP, GSN, MAP2K7 and THBS2 (p < 0.001), and GSN, KLK5 (p < 0.0001). The ontological gene analyses revealed high deregulations in gene group directly associated with breast cancer prognosis and origin.
authors.affiliation: Department of Obstetrics and Gynecology, Jessenius Faculty of Medicine, Comenius University in Bratislava, Kollarova 2 Martin, 036 01, Bratislava, Slovak Republic, Slovakia, zubor@jfmed.uniba.sk.
authors.forename: Pavol
authors.initials: P
authors.lastname: Zubor
authors.forename: Jozef
authors.initials: J
authors.lastname: Hatok
authors.forename: Petra
authors.initials: P
authors.lastname: Moricova
authors.forename: Karol
authors.initials: K
authors.lastname: Kajo
authors.forename: Ivana
authors.initials: I
authors.lastname: Kapustova
authors.forename: Andrea
authors.initials: A
authors.lastname: Mendelova
authors.forename: Peter
authors.initials: P
authors.lastname: Racay
authors.forename: Jan
authors.initials: J
authors.lastname: Danko
mesh_terms: D014408:Biomarkers, Tumor; D001940:Breast / Q000378:metabolism* / Q000473:pathology; D001943:Breast Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004848:Epithelium / Q000378:metabolism / Q000473:pathology; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D052138:Genes, Neoplasm; D020022:Genetic Predisposition to Disease; D006801:Humans; D007610:Kallikreins / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics; D011379:Prognosis; D017475:Receptors, Nerve Growth Factor / Q000235:genetics; D060765:Secretoglobins / Q000235:genetics; D059467:Transcriptome
chemical_list: D014408:Biomarkers, Tumor; C484065:NGFR protein, human; D009419:Nerve Tissue Proteins; D017475:Receptors, Nerve Growth Factor; C556464:SCGB1D2 protein, human; D060765:Secretoglobins; C512478:EGFR protein, human; D066246:ErbB Receptors; C400147:KLK5 protein, human; D007610:Kallikreins