The study of in-intro epigenetic biomarker for the early diagnosis and prognosis of breast cancer
Although therapeutic advances have improved the survival rate, most breast cancer (BC) patients still suffer from greatly reduced quality of life and even metastasis owing to delayed diagnosis. When breast cancer is detect, evaluation of prognosis is necessary to classify the more aggressive subgroup for further treatment. However, there is so far no sufficient blood based biomarker for breast cancer early detection, and the current prognostic maker also needs to be improved. Here, we performed genome-wide methylation screening using Illumina 27K and Illumina 450K array and identified a serial of differentially methylated CpG sites in the peripheral blood of BC patients. Eight genes were validated to be BC-associated by mass spectrometry in two independent validation rounds with more than 1000 subjects, and enabled a powerful discrimination of BC cases from healthy controls [area under curve (AUC) = 0.91], and was even more robust for the detection of BC in young women (age < 50, AUC = 0.95). To note, the BC-associated decreased methylation in was presented mostly in T cell fraction. Moreover, the high expression of the products of some genes was found to be significantly associated with poor prognosis of breast cancer, and was even more sufficient than the circulating tumor cells enumeration. Our study reveals a strong association between decreased DNA methylation in peripheral blood and BC, which suggested a new type of blood-based biomarker for cancer diagnosis and prognosis. The possible interaction and mechanism between tumor and circulating immune cells needs to be further studied.