Bioinformatic screening of human ESTs for differentially expressed genes in normal and tumor tissues.
BACKGROUND
Owing to the explosion of information generated by human genomics, analysis of publicly available databases can help identify potential candidate genes relevant to the cancerous phenotype. The aim of this study was to scan for such genes by whole-genome in silico subtraction using Expressed Sequence Tag (EST) data.


METHODS
Genes differentially expressed in normal versus tumor tissues were identified using a computer-based differential display strategy. Bcl-xL, an anti-apoptotic member of the Bcl-2 family, was selected for confirmation by western blot analysis.


RESULTS
Our genome-wide expression analysis identified a set of genes whose differential expression may be attributed to the genetic alterations associated with tumor formation and malignant growth. We propose complete lists of genes that may serve as targets for projects seeking novel candidates for cancer diagnosis and therapy. Our validation result showed increased protein levels of Bcl-xL in two different liver cancer specimens compared to normal liver. Notably, our EST-based data mining procedure indicated that most of the changes in gene expression observed in cancer cells corresponded to gene inactivation patterns. Chromosomes and chromosomal regions most frequently associated with aberrant expression changes in cancer libraries were also determined.


CONCLUSIONS
Through the description of several candidates (including genes encoding extracellular matrix and ribosomal components, cytoskeletal proteins, apoptotic regulators, and novel tissue-specific biomarkers), our study illustrates the utility of in silico transcriptomics to identify tumor cell signatures, tumor-related genes and chromosomal regions frequently associated with aberrant expression in cancer.
Aouacheria
Abdel
A
Laboratoire de Biométrie et Biologie Evolutive, CNRS UMR 5558, Université Claude Bernard Lyon 1, 69622 Villeurbanne Cedex, France. a.aouacheria@ibcp.fr
Navratil
Vincent
V
Barthelaix
Audrey
A
Mouchiroud
Dominique
D
Gautier
Christian
C
D000465:Algorithms; D015153:Blotting, Western; D002874:Chromosome Mapping; D002875:Chromosomes / Q000648:ultrastructure; D019295:Computational Biology / Q000379:methods*; D003627:Data Interpretation, Statistical; D030541:Databases, Genetic; D015536:Down-Regulation; D020224:Expressed Sequence Tags; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D015723:Gene Library; D015894:Genome, Human; D006801:Humans; D007633:Keratins / Q000378:metabolism; D008113:Liver Neoplasms / Q000378:metabolism; D008957:Models, Genetic; D009369:Neoplasms / Q000196:embryology / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation; D051020:bcl-X Protein / Q000096:biosynthesis / Q000235:genetics
D051020:bcl-X Protein; D007633:Keratins