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Title: Global analysis of gene expression in cervical squamous intraepithelial lesions
Author: Gooding, E. L.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2007
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The aim of this project was to investigate the gene expression profiles of SILs, using microarray technology, in order to find genes associated with their development and progression. RNA was extracted from microdissected epithelial tissue and hybridised to Affymetrix GeneChip Human Genome U133A_2 microarrays. Array data from 10 normal ectocervix, 10 LSIL and 17 HSIL samples were combined to form a high quality data set. Unsupervised hierarchical clustering of the microarray data showed that the histological diagnosis of the sample tissue was the most important factor determining gene expression profiles, since two cluster groups were formed, with one containing all normal and 4 LSIL samples, and the other all the HSIL and the remaining 6 LSIL samples. Of the more than 22 000 probe sets interrogated, 1578, 293 and 262 probe sets were differentially expressed in the HSIL – Normal, LSIL – Normal and HSIL – LSIL comparisons, respectively, whilst 1442 and 106 probe sets were differentially expressed between the two cluster groups and between the LSIL samples in each cluster group, respectively. More genes were down-regulated during the progression of SILs than were upregulated, and these genes were associated with many biological processes including cellular differentiation and cell death. Interactions with members of the activator protein-1 family, tumor necrosis factor and MYC, which showed transcriptional down-regulation, were also found to be significant for SIL progression. Potential new mechanisms of immune suppression and transcriptional disregulation in SILs were also identified. The microarray study presented in this thesis provides a valuable resource for the scientific community and genes and pathways have been identified which play significant roles in the development and progression of SILs.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available