title: Dissecting the mechanism of colorectal tumorigenesis based on RNA-sequencing data.
abstract: OBJECTIVE
  This study aimed to identify the differentially expressed genes (DEGs), mutated genes and fusion genes in colorectal cancer.
  
  
  METHODS
  RNA-sequencing data (ID: SRP009386) from cancerous, paracancerous non-tumor and distant normal tissue from one Chinese patient with stage III colorectal cancer were downloaded from Sequence Read Archive. Quality control was checked using FastQC, followed by sequence alignment against the hg19 reference genome using TopHat v1.3.3. The expression levels were quantified using Cufflinks, followed by DEGs screening using NOISeq. Enrichment analysis was performed using DAVID. Transcription factors were screened using TRANSFA. Mutated loci were identified using SAMTools and VCFTools. Gene fusion events were detected by TopHat-fusion.
  
  
  RESULTS
  In total 2440, 1887 and 834 DEGs were respectively detected in cancerous vs. normal tissue, cancerous vs. paracancerous tissue and paracancerous vs. normal tissue. The up-regulated genes from cancerous and paracancerous tissue compared with normal tissue were enriched in "extracellular matrix receptor interaction" and "focal adhesion pathway" as well as some biological processes except for "negative regulation of programmed cell death" uniquely presenting in cancer. Dysregulated transcription factors including SOX4, BCL6, CEBPB and MSX2 were enriched in the unique biological process. Trp53 was identified with one mutated locus 7577142 (C → T) on chromosome 17. BCL6 also experienced missense mutation. Additionally, COL1A1-PPP2R2C and EXPH5-COL1A2 were observed fusion genes in cancer tissue.
  
  
  CONCLUSIONS
  The unique biological process in cancer tissue may be the cause for colorectal carcinogenesis. The screened transcription factors, mutated genes and fusion genes may contribute to the progression of colorectal cancer.
authors.affiliation: Department of Gastroenterology, The Affiliated Hospital of Medical College, Qingdao University, Qingdao 266003, Shandong Province, China. Electronic address: lfuguo@yeah.net.
authors.forename: Fuguo
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of Gastroenterology, The Affiliated Hospital of Medical College, Qingdao University, Qingdao 266003, Shandong Province, China. Electronic address: jfengz@163.com.
authors.forename: Fengzhi
authors.initials: F
authors.lastname: Ji
authors.affiliation: Statistics Division, The Affiliated Hospital of Medical College, Qingdao University, Qingdao 266003, Shandong Province, China. Electronic address: xinjianghjj@163.com.
authors.forename: Yuling
authors.initials: Y
authors.lastname: Ji
authors.affiliation: Department of Gastroenterology, The Affiliated Hospital of Medical College, Qingdao University, Qingdao 266003, Shandong Province, China. Electronic address: jjyping@126.com.
authors.forename: Yueping
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Gastroenterology, The Affiliated Hospital of Medical College, Qingdao University, Qingdao 266003, Shandong Province, China. Electronic address: xguosu@163.com.
authors.forename: Xueguo
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Gastroenterology, The Affiliated Hospital of Medical College, Qingdao University, Qingdao 266003, Shandong Province, China. Electronic address: yylulan@163.com.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Gastroenterology, The Affiliated Hospital of Medical College, Qingdao University, Qingdao 266003, Shandong Province, China. Electronic address: zhlingyu@yeah.net.
authors.forename: Lingyun
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Gastroenterology, The Affiliated Hospital of Medical College, Qingdao University, Qingdao 266003, Shandong Province, China. Electronic address: hyyueh@163.com.
authors.forename: Yue
authors.initials: Y
authors.lastname: Han
authors.affiliation: Department of Gastroenterology, The Affiliated Hospital of Medical College, Qingdao University, Qingdao 266003, Shandong Province, China. Electronic address: shuangxll@163.com.
authors.forename: Xishuang
authors.initials: X
authors.lastname: Liu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D000090602:Collagen Type I, alpha 1 Chain; D015179:Colorectal Neoplasms / Q000235:genetics*; D019295:Computational Biology; D004268:DNA-Binding Proteins / Q000235:genetics; D022001:Focal Adhesions / Q000235:genetics*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D009154:Mutation; D054648:Protein Phosphatase 2 / Q000235:genetics / Q000378:metabolism; D051560:Proto-Oncogene Proteins c-bcl-6; D011956:Receptors, Cell Surface / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000235:genetics; D055751:SOXC Transcription Factors / Q000235:genetics; D016415:Sequence Alignment; D017423:Sequence Analysis, RNA; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C084103:BCL6 protein, human; D022782:CCAAT-Enhancer-Binding Protein-beta; C545012:CEBPB protein, human; D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D004268:DNA-Binding Proteins; C514892:EXPH5 protein, human; D018398:Homeodomain Proteins; C084119:MSX2 protein; C517192:PPP2R2C protein, human; D051560:Proto-Oncogene Proteins c-bcl-6; D011956:Receptors, Cell Surface; D011993:Recombinant Fusion Proteins; C083431:SOX4 protein, human; D055751:SOXC Transcription Factors; D016159:Tumor Suppressor Protein p53; C052131:extracellular matrix receptor; D054648:Protein Phosphatase 2
keywords: Colorectal cancer; Differentially expressed genes; Gene fusion; Missense mutation; RNA-sequencing; Transcription factors