Screening of Breast Cancer Methylation Biomarkers Based on the TCGA Database.

OBJECTIVE: Breast cancer has become a fatal disease for women world-wide. Its incidence in China has been increasing yearly, and the identification of early-stage biomarkers is urgently required. METHODS: ANOVA was carried out in the case of a primary tumor, adjacent normal tissue, and tumor metastasis of breast cancer, and on pan-cancer samples using the genome-wide methylation data of 31 solid tumor Illumina Methylation 450K chips downloaded from The Cancer Genome Atlas (TCGA) website in September 2018. Methylation sites showing a significant difference (P ≤ 0.05) were screened and compared with the whole-genome methylation data of 31 other solid tumor species in the TCGA database using t-tests in order to screen the methylation sites of breast cancer-specific expression. The expression of the screened methylation sites was confirmed through pyrosequencing in 45 cases of breast cancer, lung cancer, gastric cancer, and colorectal cancer. RESULTS: A total of 10 specific breast cancer methylation sites (cg13683194, cg07996594, cg21646032, cg07671949, cg21185686, cg03625109, cg16429070, cg23601468, cg24818566, and cg01240931) were analyzed; nine genes (C9orf125, RARB, ESR1, RUNX3, PCDHGB7, DBC1, PDGFRB, TIMP3, and APC) were involved. The overall effect was excellent; a total of 4 methylation sites (2 in the DBC1 gene [cg03625109 and cg24818566], 1 in the C9orf125 gene [cg13683194], and 1 in the PDGFRB gene [cg16429070]) could effectively distinguish breast cancer from 31 other cancer species. The pyrosequencing results revealed that 7 screened methylation sites could significantly distinguish between breast cancer, lung cancer, gastric cancer, and colorectal cancer samples; these sites could also specifically distinguish between luminal A, luminal B, HER2, and Basal-like types of breast cancer. CONCLUSION: The 10 breast cancer methylation sites screened in the present study can effectively distinguish breast cancer from 31 other solid tumors, and they are expected to be used as biomarkers for early screening of breast cancer.