title: Expression profile of MAGI2 gene as a novel biomarker in combination with major deregulated genes in prostate cancer.
abstract: Complex molecular changes that occur during prostate cancer (PCa) progression have been described recently. Whole genome sequencing of primary PCa samples has identified recurrent gene deletions and rearrangements in PCa. Specifically, these molecular events disrupt the gene loci of phosphatase and tensin homolog (PTEN) and membrane-associated guanylate kinase inverted-2 (MAGI2). In the present study, we analyzed the expression profile of MAGI2 gene in a cohort of clinical PCa (n = 45) and benign prostatic hyperplasia (BPH) samples (n = 36) as well as three PCa cell lines. We also studied the expression of PCa-related genes, including PTEN, NKX3.1, SPINK1, DD3, AMACR, ERG, and TMPRSS2-ERG fusion in the same samples. The expression of MAGI2 mRNA was significantly down-regulated in PC3, LNCaP and DU-145 PCa cell lines (p = 0.000), and also in clinical tumor samples (Relative expression = 0.307, p = 0.002, [95 % CI 0.002-12.08]). The expression of PTEN, NKX3.1, SPINK1, DD3, and AMACR genes was significantly deregulated in prostate tumor samples (p range 0.000-0.044). A significant correlation was observed between MAGI2 and NKX3.1 expression in tumor samples (p = 0.006). Furthermore, the inclusion of MAGI2 in the gene panel improved the accuracy for discrimination between PCa and BPH samples with the sensitivity and specificity of 0.88 [CI 0.76-0.95] and 0.83 [CI 0.68-0.92], respectively. The data presented here suggest that MAGI2 gene can be considered as a novel component of gene signatures for the detection of PCa.
authors.affiliation: Molecular Medicine Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, 1316943551, Iran, dr.reza.mahdian@gmail.com.
authors.forename: Reza
authors.initials: R
authors.lastname: Mahdian
authors.forename: Vahideh
authors.initials: V
authors.lastname: Nodouzi
authors.forename: Mojgan
authors.initials: M
authors.lastname: Asgari
authors.forename: Mitra
authors.initials: M
authors.lastname: Rezaie
authors.forename: Javad
authors.initials: J
authors.lastname: Alizadeh
authors.forename: Behzad
authors.initials: B
authors.lastname: Yousefi
authors.forename: Hossein
authors.initials: H
authors.lastname: Shahrokh
authors.forename: Maryam
authors.initials: M
authors.lastname: Abolhasani
authors.forename: Mohamadreza
authors.initials: M
authors.lastname: Nowroozi
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000368:Aged; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D018450:Disease Progression; D015536:Down-Regulation; D017353:Gene Deletion; D015972:Gene Expression Regulation, Neoplastic; D005819:Genetic Markers; D051528:Guanylate Kinases; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007492:Iran; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism; D011467:Prostate / Q000166:cytology / Q000473:pathology; D011470:Prostatic Hyperplasia / Q000235:genetics; D011471:Prostatic Neoplasms / Q000235:genetics*; D019998:Racemases and Epimerases / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D000071230:Transcriptional Regulator ERG; D059467:Transcriptome; D014359:Trypsin Inhibitor, Kazal Pancreatic
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000951:Antigens, Neoplasm; D002352:Carrier Proteins; C072312:ERG protein, human; D005819:Genetic Markers; D018398:Homeodomain Proteins; D008565:Membrane Proteins; C491178:NKX3-1 protein, human; C486642:SPINK1 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D000071230:Transcriptional Regulator ERG; C479341:prostate cancer antigen 3, human; D014359:Trypsin Inhibitor, Kazal Pancreatic; D051528:Guanylate Kinases; C485777:MAGI2 protein, human; C446603:TPTE protein, human; D051059:PTEN Phosphohydrolase; D019998:Racemases and Epimerases; C108352:alpha-methylacyl-CoA racemase