Author:
Steinau Martin,Lee Daisy R,Rajeevan Mangalathu S,Vernon Suzanne D,Ruffin Mack T,Unger Elizabeth R
Abstract
Abstract
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.
Conclusion
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.
Publisher
Springer Science and Business Media LLC
Reference16 articles.
1. Habis AH, Vernon SD, Lee DR, Verma M, Unger ER: Molecular quality of exfoliated cervical cells: implications for molecular epidemiology and biomarker discovery. Cancer Epidemiol Biomarkers Prev. 2004, 13: 492-496.
2. Spivack SD, Hurteau GJ, Jain R, Kumar SV, Aldous KM, Gierthy JF, Kaminsky LS: Gene-environment interaction signatures by quantitative mRNA profiling in exfoliated buccal mucosal cells. Cancer Res. 2004, 64: 6805-6813.
3. Klaassen I, Copper MP, Brakenhoff RH, Smeets SJ, Snow GB, Braakhuis BJ: Exfoliated oral cell messenger RNA: suitability for biomarker studies. Cancer Epidemiol Biomarkers Prev. 1998, 7: 469-472.
4. Ranamukhaarachchi DG, Unger ER, Vernon SD, Lee DR, Rajeevan MS: Gene expression profiling of dysplastic differentiation in cervical epithelial cell harboring HPV 16. Genomics. 2005, in press:
5. Tabor MP, Brakenhoff RH, Ruijter-Schippers HJ, Kummer JA, Leemans CR, Braakhuis BJ: Genetically altered fields as origin of locally recurrent head and neck cancer: a retrospective study. Clin Cancer Res. 2004, 10: 3607-3613.
Cited by
16 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献