New approaches to functional process discovery in HPV 16-associated cervical cancer cells by gene ontology

Abstract

Purpose: This study utilized both mRNA differential display and the Gene Ontology (GO) analysis to characterize the multiple interactions of a number of genes with gene expression profiles involved in the HPV-16- induced cervical carcinogenesis. Materials and Methods: mRNA differential displays, with HPV-16 positive cervical cancer cell line (SiHa), and normal human keratinocyte cell line (HaCaT) as a control, were used. Each human gene has several biological functions in the Gene Ontology; therefore, several functions of each gene were chosen to establish a powerful cervical carcinogenesis pathway. The specific functions assigned to these genes were then correlated with the gene expression patterns. Results: The results showed that 157 genes were up- or down-regulated at least 2-fold and organized into reciprocally dependent sub-function sets, depending on their cervical cancer pathway, suggesting the potentially significant genes of unknown function affected by the HPV-16-derived pathway. The GO analysis suggested that the cervical cancer cells underwent repression of the cancer-specific cell adhesive properties. Also, genes belonging to DNA metabolism, such as DNA repair and replication, were strongly down-regulated, whereas significant increases were shown in the protein degradation and synthesis. Conclusion: The GO analysis can overcome the complexity of the gene expression profile of the HPV-16- associated pathway, identify several cancer-specific cellular processes and genes of unknown function. It could also become a major competing platform for the genome- wide characterization of carcinogenesis.