High expression of DNMT1 in breast invasive carcinoma associated with tumor immune microenvironment and poor prognosis

(1) Background: Interleukin-6 (IL-6) is a multifunctional cytokine that was found to cause epigenetic changes by regulating DNA methyltransferase 1 (DNMT1). IL-6 has al-so been found to promote tumor progression and chemoresistance in numerous types of cancers. However, it remains unknown how IL-6 and DNMT1 may impact prognosis in different breast cancer types. (2) Methods: Patient survival rate in breast cancer patients and DNMT1 expression pattern was examined in TCGA datasets. Protein expression pattern of IL-6 and DNMT1 were investigated in the tissue microarray in our cohort (n=285, Show Chwan Memorial Hospital, Changhua) by immunohistochemistry (IHC). IL-6 and DNMT1 expressions were examined in breast cancer cell-lines. Cell invasion activity was compared between high and low IL-6/DNMT expressing breast cancer cell lines, and between cells treated with/without IL-6 antibody. (3) Results: DNMT1 mRNA level was significantly higher in the breast tumor tissues (p (4) Conclusions: IL-6-DNMT1 axis could be responsible for HER2-positive breast cancer progression in tumor immune microenvironment. Our study suggests that IL-6 inhibition in combination with anti-HER2 therapy might be an effective approach in particular for HER2-positive patients with a potential to become a standard therapeutic strategy.