A transcriptome anatomy of human colorectal cancers
Bingjian Lü1, Jing Xu1, Maode Lai1, Hao Zhang2 and Jian Chen1
1Department of Pathology & Pathophysiology, School of Medicine, Zhejiang University, PR , 310031, China
2Department of Computer Science, School of Computer Science & Technology, Zhejiang University, PR, 310023, China
BMC Cancer 2006,
6:40. This is an Open Access article distributed under the terms of the Creative Commons Attribution License.
Abstract
Background
Accumulating databases in human genome research have enabled
integrated genome-wide study on complicated diseases such as cancers. A
practical approach is to mine a global transcriptome profile of disease
from public database. New concepts of these diseases might emerge by
landscaping this profile.
Methods
In this study, we clustered human colorectal normal mucosa (N),
inflammatory bowel disease (IBD), adenoma (A) and cancer (T) related
expression sequence tags (EST) into UniGenes via an in-house GetUni
software package and analyzed the transcriptome overview of these
libraries by GOTree Machine (GOTM). Additionally, we downloaded UniGene
based cDNA libraries of colon and analyzed them by Xprofiler to cross
validate the efficiency of GetUni. Semi-quantitative RT-PCR was used to
validate the expression of β-catenin and. 7 novel genes in colorectal cancers.
Results
The efficiency of GetUni was successfully validated by Xprofiler and
RT-PCR. Genes in library N, IBD and A were all found in library T. A
total of 14,879 genes were identified with 2,355 of them having at
least 2 transcripts. Differences in gene enrichment among these
libraries were statistically significant in 50 signal transduction
pathways and Pfam protein domains by GOTM analysis P < 0.01
Hypergeometric Test). Genes in two metabolic pathways, ribosome and
glycolysis, were more enriched in the expression profiles of A and IBD
than in N and T. Seven transmembrane receptor superfamily genes were
typically abundant in cancers.
Conclusion
Colorectal cancers are genetically heterogeneous. Transcription
variants are common in them. Aberrations of ribosome and glycolysis
pathway might be early indicators of precursor lesions in colon
cancers. The electronic gene expression profile could be used to
highlight the integral molecular events in colorectal cancers.