Screening for differentially methylated genes among human colorectal cancer tissues and normal mucosa by microarray chip
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Screening for differentially methylated genes among human colorectal cancer tissues and normal mucosa by microarray chip Wei Chen • Jun Xiang • De-Feng Chen • Bei-Bei Ni • Hao Chen • Xin-Juan Fan Pu-Ning Wang • Shun-Xin Song • Le-Kun Fang • Huan-Yu Xiao • Lei Wang • Jian-Ping Wang
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Received: 28 March 2012 / Accepted: 1 October 2012 / Published online: 8 March 2013 Springer Science+Business Media Dordrecht 2013
Abstract High density DNA methylation microarrays were used to study the differences of gene methylation level in six pairs of colorectal cancer (CRC) and adjacent normal mucosa. We analyzed the profile of methylated genes by NimbleGen Microarray and the biologic functions by NIH-NAVID. In addition, preliminary validation studies were done in six pairs of samples by MSP (methylationspecific PCR). A total of 4,644 genes had a difference in methylation levels. Among them 2,296 were hypermethylated (log2ratio [ 1), 2,348 genes were hypomethylated (log2ratio \ -1), in which 293 hypermethylated and 313 hypomethylated genes were unmapped according to the NIH-NAVID. All these genes were randomly distributed on all the chromosomes. However, chromosome 1 contained the most of the hypermethylated genes (232 genes), followed by chromosome 19 (149 genes), chromosome 11 (144 genes), chromosome 2 (141 genes), chromosomes 3 (127 genes). Through the analysis of the statistics, There were 2 hypermethylated/3 hypomethylated genes involved in six pairs of samples simultaneously, followed by 10/14 in five samples, 34/37 in four samples, 101/113 in three W. Chen J. Xiang D.-F. Chen H. Chen P.-N. Wang S.-X. Song L.-K. Fang L. Wang (&) J.-P. Wang (&) Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, 26 Yuancunerheng Rd, Guangzhou, Guangdong 510655, People’s Republic of China e-mail: [email protected] J.-P. Wang e-mail: [email protected] B.-B. Ni X.-J. Fan Institute of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, Guangdong, China H.-Y. Xiao Sun Yat-sen University, Guangzhou 510655, Guangdong, China
samples, 341/377 in two samples, 1,808/1,804 in one sample. According to gene ontology analysis, some physiological processes play important roles in the cell division and the development of tumor, such as apoptosis, DNA repair, immune, cell cycle, cell cycle checkpoint, cell adhesion and invasion etc. Through Preliminary validation, there were two genes (St3gal6, Opcml) in thirty top-ranking genes shown hypermethylated in six pairs of CRC and adjacent normal mucosa. Conclusions High density DNA methylation microarrays is an effective method for screening aberrantly methylated genes in CRC. The methylated genes should be further studied for diagnostic or prognostic markers for CRC. Keywords Methylation Colorectal cancer Microarray Epigenetics
Introduction Colorectal cancer (CRC) is the third most common cancer in the world, the mortality has remained the same for the past 50 years. Despite advances in diagnosis and
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