Gene expression profile of cervical tissue compared to exfoliated cells: impact on biomarker discovery.
BACKGROUND
Exfoliated cervical cells are used in cytology-based cancer screening and may also be a source for molecular biomarkers indicative of neoplastic changes in the underlying tissue. However, because of keratinization and terminal differentiation it is not clear that these cells have an mRNA profile representative of cervical tissue, and that the profile can distinguish the lesions targeted for early detection.


RESULTS
We used whole genome microarrays (25,353 unique genes) to compare the transcription profiles from seven samples of normal exfoliated cells and one cervical tissue. We detected 10,158 genes in exfoliated cells, 14,544 in the tissue and 7320 genes in both samples. For both sample types the genes grouped into the same major gene ontology (GO) categories in the same order, with exfoliated cells, having on average 20% fewer genes in each category. We also compared microarray results of samples from women with cervical intraepithelial neoplasia grade 3 (CIN3, n = 15) to those from age and race matched women without significant abnormalities (CIN1, CIN0; n = 15). We used three microarray-adapted statistical packages to identify differential gene expression. The six genes identified in common were two to four fold upregulated in CIN3 samples. One of these genes, the ubiquitin-conjugating enzyme E2 variant 1, participates in the degradation of p53 through interaction with the oncogenic HPV E6 protein.


CONCLUSIONS
The findings encourage further exploration of gene expression using exfoliated cells to identify and validate applicable biomarkers. We conclude that the gene expression profile of exfoliated cervical cells partially represents that of tissue and is complex enough to provide potential differentiation between disease and non-disease.
Steinau
Martin
M
Centers for Disease Control and Prevention, Atlanta, GA, USA. MSteinau@cdc.gov
Lee
Daisy R
DR
Rajeevan
Mangalathu S
MS
Vernon
Suzanne D
SD
Ruffin
Mack T
MT
Unger
Elizabeth R
ER
D015415:Biomarkers; D014408:Biomarkers, Tumor; D002584:Cervix Uteri / Q000378:metabolism*; D019295:Computational Biology / Q000379:methods; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D005819:Genetic Markers; D015894:Genome, Human; D023281:Genomics / Q000379:methods; D006801:Humans; D007633:Keratins / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000378:metabolism; D012984:Software; D014158:Transcription, Genetic; D015854:Up-Regulation; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D002578:Uterine Cervical Dysplasia / Q000235:genetics / Q000473:pathology
D015415:Biomarkers; D014408:Biomarkers, Tumor; D005819:Genetic Markers; D012333:RNA, Messenger; D007633:Keratins