mRNA/microRNA gene expression profile in microsatellite unstable colorectal cancer.
BACKGROUND
Colorectal cancer develops through two main genetic instability pathways characterized by distinct pathologic features and clinical outcome.


RESULTS
We investigated colon cancer samples (23 characterized by microsatellite stability, MSS, and 16 by high microsatellite instability, MSI-H) for genome-wide expression of microRNA (miRNA) and mRNA. Based on combined miRNA and mRNA gene expression, a molecular signature consisting of twenty seven differentially expressed genes, inclusive of 8 miRNAs, could correctly distinguish MSI-H versus MSS colon cancer samples. Among the differentially expressed miRNAs, various members of the oncogenic miR-17-92 family were significantly up-regulated in MSS cancers. The majority of protein coding genes were also up-regulated in MSS cancers. Their functional classification revealed that they were most frequently associated with cell cycle, DNA replication, recombination, repair, gastrointestinal disease and immune response.


CONCLUSIONS
This is the first report that indicates the existence of differences in miRNA expression between MSS versus MSI-H colorectal cancers. In addition, the work suggests that the combination of mRNA/miRNA expression signatures may represent a general approach for improving bio-molecular classification of human cancer.
Lanza
Giovanni
G
Department of Experimental and Diagnostic Medicine and Interdepartment Center for Cancer Research, University of Ferrara, Ferrara, Italy. lng@unife.it
Ferracin
Manuela
M
Gafà
Roberta
R
Veronese
Angelo
A
Spizzo
Riccardo
R
Pichiorri
Flavia
F
Liu
Chang-gong
CG
Calin
George A
GA
Croce
Carlo M
CM
Negrini
Massimo
M
D000368:Aged; D015179:Colorectal Neoplasms / Q000145:classification* / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D035683:MicroRNAs / Q000032:analysis*; D053842:Microsatellite Instability; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000032:analysis*; D012334:RNA, Neoplasm / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D035683:MicroRNAs; D012333:RNA, Messenger; D012334:RNA, Neoplasm
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