Updated: Jun 15
The Innovation and Validation of CPG Island Methylator Phenotype-Associated Prognosis Model for Breast Cancer
Author : Linyue Lu
Affiliated High School of South China Normal University, Guangzhou, Guangdong, China
Though being the most prevalent malignancy, breast cancer lacks effective prevention measures, which renders therapies and prognosis essential. The CPG island methylator phenotype (CIMP), a common biological phenomenon, has important implications in cancer progression. However, in breast cancer, the mechanism by which CIMP affects tumor progression and the associated clinical features has not yet been investigated.
The DNA methylation inhibitor was applied to two breast cancer cell lines with significantly different phenotypes with those of normal cells, which verifies that the tumor cell activities are affected to a greater extent under low DNA methylation levels. Thus, in this research, DNA methylation data of breast cancer from the TCGA database was used to evaluate the correlation between methylation phenotype and clinical performance. A total of 895 tumor samples were classified into three subtypes (CIMP-H, CIMP-M and CIMP-L) based on methylation levels. Combined with clinical data, the CIMP was found significantly associated with survival. Also, immune cells differ between CIMP categories, and further analysis identified genes with different mutation rates between groups. Finally, enrichment analysis was done for genes differentially expressed between groups. Determined by 18 genes, the CIMP-associated prognostic model (CPM) was further constructed using the enrichment pathways of genes with high expression in each group, and CPM score was obtained as the risk score.
The analysis revealed that a high CPM risk score corresponded to a poorer prognosis and that CPM, stage, age, and Pathologic_N, Pathologic_M were significantly associated with survival and prognosis.