High expression of
insulin-like growth factor-II (
IGF-II) in
epithelial ovarian cancer is associated with aggressive disease and poor prognosis.
IGF-II transcription is initiated from multiple promoters. Promoter-specific expression is regulated by DNA methylation, which is often dysregulated in
cancer. Here, the effects of promoter-specific methylation on
IGF-II expression are investigated in
ovarian cancer. Fresh
tumor samples were collected from 211 patients for analyses of
IGF-II promoter methylation using methylation-specific PCR, and of promoter-specific expression of
IGF-II mRNA with qRT-PCR, as well as tissue levels of
IGF-II peptide with an ELISA. Cox regression analysis was performed to assess
IGF-II methylation and expression in association with progression-free and overall survival. DNA methylation was high in
IGF-II promoters 2 (P2, 64.2%) and 3 (P3, 52.1%) and low in promoter 4 (P4, 9.8%). High methylation was associated with low
mRNA expression in a promoter-specific manner. P3 methylation and expression appeared to be critical in
ovarian cancer compared to other promoters. While methylation in an individual promoter was not associated with the disease, a methylation pattern involving P2 and P3 was significantly different among patients with distinct
tumor grade, debulking results,
residual tumor size and treatment response. The methylation pattern was also associated with
disease progression. The study suggests that DNA methylation regulates
IGF-II promoter-specific expression in
ovarian cancer and the regulation may play a role in
disease progression. Assessing methylation patterns in
IGF-II promoters may have clinical implications.