Dissecting the mechanism of colorectal tumorigenesis based on RNA-sequencing data

Abstract

ObjectiveThis study aimed to identify the differentially expressed genes (DEGs), mutated genes and fusion genes in colorectal cancer. Materials and methodsRNA-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. ResultsIn 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. ConclusionsThe 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.