Identification of Novel Epigenetic Markers of Prostate Cancer by NotI-Microarray Analysis

被引:38
作者
Dmitriev, Alexey A. [1 ,2 ]
Rosenberg, Eugenia E. [3 ]
Krasnov, George S. [1 ]
Gerashchenko, Ganna V. [3 ]
Gordiyuk, Vasily V. [3 ]
Pavlova, Tatiana V. [4 ]
Kudryavtseva, Anna V. [1 ]
Beniaminov, Artemy D. [1 ]
Belova, Anastasia A. [1 ]
Bondarenko, Yuriy N. [5 ]
Danilets, Rostislav O. [5 ]
Glukhov, Alexander I. [6 ]
Kondratov, Aleksandr G. [3 ]
Alexeyenko, Andrey [7 ]
Alekseev, Boris Y. [2 ]
Klein, George [4 ]
Senchenko, Vera N. [1 ]
Kashuba, Vladimir I. [3 ,4 ]
机构
[1] Russian Acad Sci, VA Engelhardt Mol Biol Inst, Moscow 119991, Russia
[2] Minist Healthcare Russian Federat, PA Herzen Moscow Canc Res Inst, Moscow 125284, Russia
[3] Natl Acad Sci Ukraine, Inst Mol Biol & Genet, UA-03680 Kiev, Ukraine
[4] Karolinska Inst, Dept Microbiol Tumor & Cell Biol, S-17177 Stockholm, Sweden
[5] Natl Acad Med Sci Ukraine, Inst Urol, UA-04053 Kiev, Ukraine
[6] Kurchatov NBIC Ctr NRC, Kurchatov Inst, Dept Mol Biol, Moscow 123182, Russia
[7] Karolinska Inst, Sci Life Lab, Bioinformat Infrastruct Life Sci, S-17177 Stockholm, Sweden
基金
俄罗斯基础研究基金会;
关键词
DNA METHYLATION MARKERS; SET ENRICHMENT ANALYSIS; CHROMOSOME; 3; PROMOTER METHYLATION; GENE; EXPRESSION; AGGRESSIVENESS; LOCI; ASSOCIATION; METASTASIS;
D O I
10.1155/2015/241301
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
A significant need for reliable and accurate cancer diagnostics and prognosis compels the search for novel biomarkers that would be able to discriminate between indolent and aggressive tumors at the early stages of disease. The aim of this work was identification of potential diagnostic biomarkers for characterization of different types of prostate tumors. NotI-microarrays with 180 clones associated with chromosome 3 genes/loci were applied to determine genetic and epigenetic alterations in 33 prostate tumors. For 88 clones, aberrations were detected in more than 10% of tumors. The major types of alterations were DNA methylation and/or deletions. Frequent methylation of the discovered loci was confirmed by bisulfite sequencing on selective sampling of genes: FGF12, GATA2, and LMCD1. Three genes (BHLHE40, BCL6, and ITGA9) were tested for expression level alterations using qPCR, and downregulation associated with hypermethylation was shown in the majority of tumors. Based on these data, we proposed the set of potential biomarkers for detection of prostate cancer and discrimination between prostate tumors with different malignancy and aggressiveness: BHLHE40, FOXP1, LOC285205, ITGA9, CTDSPL, FGF12, LOC440944/SETD5, VHL, CLCN2, OSBPL10/ZNF860, LMCD1, FAM19A4, CAND2, MAP4, KY, and LRRC58. Moreover, we probabilistically estimated putative functional relations between the genes within each set using the network enrichment analysis.
引用
收藏
页数:13
相关论文
共 72 条
[1]   Androgen deprivation therapy for prostate cancer: long-term safety and patient outcomes [J].
Ahmadi, Hamed ;
Daneshmand, Siamak .
PATIENT-RELATED OUTCOME MEASURES, 2014, 5 :63-70
[2]   Network enrichment analysis: extension of gene-set enrichment analysis to gene networks [J].
Alexeyenko, Andrey ;
Lee, Woojoo ;
Pernemalm, Maria ;
Guegan, Justin ;
Dessen, Philippe ;
Lazar, Vladimir ;
Lehtio, Janne ;
Pawitan, Yudi .
BMC BIOINFORMATICS, 2012, 13
[3]   Global networks of functional coupling in eukaryotes from comprehensive data integration [J].
Alexeyenko, Andrey ;
Sonnhammer, Erik L. L. .
GENOME RESEARCH, 2009, 19 (06) :1107-1116
[4]  
[Anonymous], 2012, Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012
[5]   Folliculin Contributes to VHL Tumor Suppressing Activity in Renal Cancer through Regulation of Autophagy [J].
Bastola, Prabhat ;
Stratton, Yiwen ;
Kellner, Emily ;
Mikhaylova, Olga ;
Yi, Ying ;
Sartor, Maureen A. ;
Medvedovic, Mario ;
Biesiada, Jacek ;
Meller, Jarek ;
Czyzyk-Krzeska, Maria F. .
PLOS ONE, 2013, 8 (07)
[6]   Two susceptibility loci identified for prostate cancer aggressiveness [J].
Berndt, Sonja I. ;
Wang, Zhaoming ;
Yeager, Meredith ;
Alavanja, Michael C. ;
Albanes, Demetrius ;
Amundadottir, Laufey ;
Andriole, Gerald ;
Freeman, Laura Beane ;
Campa, Daniele ;
Cancel-Tassin, Geraldine ;
Canzian, Federico ;
Cornu, Jean-Nicolas ;
Cussenot, Olivier ;
Diver, W. Ryan ;
Gapstur, Susan M. ;
Gronberg, Henrik ;
Haiman, Christopher A. ;
Henderson, Brian ;
Hutchinson, Amy ;
Hunter, David J. ;
Key, Timothy J. ;
Kolb, Suzanne ;
Koutros, Stella ;
Kraft, Peter ;
Le Marchand, Loic ;
Lindstroem, Sara ;
Machiela, Mitchell J. ;
Ostrander, Elaine A. ;
Riboli, Elio ;
Schumacher, Fred ;
Siddiq, Afshan ;
Stanford, Janet L. ;
Stevens, Victoria L. ;
Travis, Ruth C. ;
Tsilidis, Konstantinos K. ;
Virtamo, Jarmo ;
Weinstein, Stephanie ;
Wilkund, Fredrik ;
Xu, Jianfeng ;
Zheng, S. Lilly ;
Yu, Kai ;
Wheeler, William ;
Zhang, Han ;
Consortium, African Ancestry Prostate Canc G. W. A. S. ;
Sampson, Joshua ;
Black, Amanda ;
Jacobs, Kevin ;
Hoover, Robert N. ;
Tucker, Margaret ;
Chanock, Stephen J. .
NATURE COMMUNICATIONS, 2015, 6
[7]   Molecular Diagnosis of Prostate Cancer: Are We Up to Age? [J].
Bhavsar, Tapan ;
McCue, Peter ;
Birbe, Ruth .
SEMINARS IN ONCOLOGY, 2013, 40 (03) :259-275
[8]   HTRIdb: an open-access database for experimentally verified human transcriptional regulation interactions [J].
Bovolenta, Luiz A. ;
Acencio, Marcio L. ;
Lemke, Ney .
BMC GENOMICS, 2012, 13
[9]  
Campbell C, 2011, Learning with Support Vector Machines
[10]   Somatic LMCD1 mutations promoted cell migration and tumor metastasis in hepatocellular carcinoma [J].
Chang, C-Y ;
Lin, S-C ;
Su, W-H ;
Ho, C-M ;
Jou, Y-S .
ONCOGENE, 2012, 31 (21) :2640-2652