Values of 5mC, 5hmC, and TET2 for identifying the presence and progression of breast precancerous lesion

Abstract

This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. AbstractBackground: This study aimed to evaluate the correlations of 5-methylcytosine (5mC), 5-hydroxymethylcytosine (5hmC), and ten-eleven translocation enzyme 2 (TET2) expressions in lesion tissue with histological classification of breast precancerous lesion. Methods:Eighty-three patients with breast ductal intraepithelial neoplasia (DIN), 20 patients with breast ductal carcinoma in situ with microinvasion (DCIS-MI), and 10 patients with invasive breast cancer were included. Histological classification of the DIN patients was classified as DIN1A, DIN1B, DIN1C, DIN2, and DIN3. 5mC, 5hmC, and TET2 expressions in lesion tissues from biopsy were assessed by immunohistochemistry (IHC) assay.Results: 5hmC and TET2 were negatively associated with histological classification as validated by both IHC score and IHC semi-quantification expression grades in total patients (all P < .05); however, no correlation of 5mC with histological classification was found (all P > .05). 5mC (P = .004) was negatively but 5hmC (P < .001) was positively correlated with TET2, while no association of 5mC with 5hmC was discovered in total patients (P = .078). In addition, 5mC was positively associated with ER expression in total patients (P = .040). In subgroups, 5mC was negatively correlated with 5hmC in DIN1C patients (P = .023) and invasive cancer patients (P = .044), and 5mC was negatively associated with TET2 in DIN1B patients (P = .004) as well as DCIS-MI patients (P = .003).Conclusion: 5hmC and TET2 have the potentials to serve as biomarkers that could assist in the identification of presence and progression of breast precancerous lesion. K E Y W O R D S5-methylcytosine, 5-hydroxymethylcytosine, biomarker, breast precancerous lesion, teneleven translocation enzyme 2 1 | INTRODUC TI ON Breast cancer, the most frequent cancer in women worldwide, attacks approximately 2 088 849 patients and results in roughly 626 679 related deaths in 2018. 1 Breast cancer is featured by the heterogeneous molecular subtypes, such as luminal A, luminal B, human epidermal growth factor receptor 2 (HER2) enriched type, and basal-like breast cancer, which is closely related to the therapeutic decision-making and prognosis in clinical setting. 2 In Asia, an elevation of breast cancer incidence could be seen as a R E FE R E N C E S How to cite this article: Zhang Z, Jin Y, Zhang W, et al. Values of 5mC, 5hmC, and TET2 for identifying the presence and progression of breast precancerous lesion. J Clin Lab Anal.

TET2 Promotes Keloid Hyperplasia by Regulating 5hmC Modification in the TGFβ Promoter Region

“…This strongly suggested that TET2 regulates keloid growth by the proliferation of HKFs. Similarly, previous studies have also found that TET2 is involved in the occurrence of breast cancer, 16 glioma 17 and other cancers. Furthermore, TET2 affects tumour formation by regulating the proliferation process of cancer cells.…”

TET Enzymes and 5hmC Levels in Carcinogenesis and Progression of Breast Cancer: Potential Therapeutic Targets

“…Its low expression correlates with poor OS, Relapse-Free Survival (RFS), Post-Progression Survival (PPS), advanced stage, lymph node metastasis, high tumor grade, and aberrant methylation in its promoter in BC patients [ 28 , 33 , 39 , 40 , 41 , 42 ]. Low TET2 expression negatively correlates with the histological classification of BC lesions, activated CD8 + T cells, CD56 + natural killer cells, gamma delta T cells, macrophages, myeloid-derived suppressor cells (MDSC), and monocytes and positively correlates with 5hmC levels, immune-infiltrating tumor-associated fibroblast, and memory B cells [ 41 , 43 ]. In contrast, other studies showed that TET2 expression is increased in lymph node metastasis, BC tissue samples, and MCF-7 BC cells compared with metastasis-negative, normal tissue samples and HBL-100 untransformed immortalized cells [ 36 , 44 , 45 ].…”

“…Low 5hmC levels correlate with poor cell differentiation, Disease-Specific Survival (DSS), and DFS in BC patients, including the ER/PR negative subtypes [ 30 ]. Moreover, the levels of this epigenetic mark negatively correlate with the histological classification of BC lesions and positively correlate with TET2 expression [ 43 ]. The 5hmC levels are increased, while the 5mC levels are decreased in tumorspheres obtained from MCF-7 cells.…”

Deoxyribonucleic Acid 5-Hydroxymethylation in Cell-Free Deoxyribonucleic Acid, a Novel Cancer Biomarker in the Era of Precision Medicine

“…Jankowska et al, 2015), and has been reported in the process of multiple precancerous pathogenesis. For instance, the increase and decrease of 5hmC level were respectively associated with the cervical precancerous lesions (Su et al, 2019) and the breast precancerous lesions (Zhang et al, 2020). 5hmC was also involved in hepatocellular carcinoma (HCC), melanoma and esophageal cancer (Lian et al, 2012;Tian et al, 2018;Liu et al, 2019a;Krais et al, 2019).…”