Balasubramaniam, Shandra Devi
(2022)
Genomic Expression Profile Of Human Papillomavirus 16 And 18 – Associated Pre-cancerous Lesions And Cancer Of The Cervix.
PhD thesis, Universiti Sains Malaysia.
Abstract
Cervical cancer is one of the most common cancers in women and is caused by high-risk human papillomavirus (HPV) infection. The integration of HPV into host cervical epithelial cells causes genetic alterations and consequent changes in gene expression affecting downstream molecular pathways, leading to the development of cervical cancer. This study aimed to profile the genomic signatures involved in the pathogenesis of HPV 16 and 18 associated pre-cancerous lesions (cervical intraepithelial neoplasia, CIN) and squamous cell carcinoma (SCC) of the cervix, in comparison to the normal cervix. The differential mRNA expression profiles were determined, to evaluate the expression of up-regulated and down-regulated host genes and to evaluate the perturbed molecular pathways involved in cervical carcinogenesis. In this study, 29 formalin-fixed paraffin-embedded (FFPE) tissues including low-grade CIN (LGCIN), high-grade CIN (HGCIN), SCC, and normal cervix were screened for HPV 16 and HPV 18 using immunohistochemistry and qRT-PCR method. Of these, 9 HPV-positive (3 LGCIN, 3 HGCIN, 3 SCC) and 3 normal cervix (HPV-negative) tissue samples were microdissected to obtain regions of interest in the squamous epithelium before RNA extraction. Transcriptomic profiling was performed using the Affymetrix, GeneChip Human Transcriptome Array 2.0 (HTA 2.0) and the nCounter® PanCancer Pathway Array, Nanostring to identify differentially expressed genes (DEGs) and significantly associated pathways in each stage of cervical cancer development.
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