IGF-II promoter specific methylation and expression in epithelial ovarian cancer and their associations with disease characteristics.

Abstract

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.

• Authors: Biyun Qian, Dionyssios Katsaros, Lingeng Lu, Emilie Marion Canuto, Chiara Benedetto, Alicia Beeghly-Fadiel, Herbert Yu
• Journal: Oncology reports (Oncol Rep) Vol. 25 Issue 1 Pg. 203-13 (Jan 2011) ISSN: 1791-2431 [Electronic] Greece
• PMID: 21109978 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Insulin-Like Growth Factor II

Topics

• Adult
• Aged
• Aged, 80 and over
• DNA Methylation (genetics)
• Disease-Free Survival
• Female
• Gene Expression Regulation, Neoplastic (genetics)
• Humans
• Insulin-Like Growth Factor II (biosynthesis, genetics)
• Middle Aged
• Neoplasm Staging
• Neoplasms, Glandular and Epithelial (genetics, mortality, pathology)
• Ovarian Neoplasms (genetics, mortality, pathology)
• Promoter Regions, Genetic (genetics)
• Reverse Transcriptase Polymerase Chain Reaction