AUTHOR=Ansar Muhamad , Thu Le Thi Anh , Hung Chin-Sheng , Su Chih-Ming , Huang Man-Hsu , Liao Li-Min , Chung Yu-Mei , Lin Ruo-Kai 

TITLE=Promoter hypomethylation and overexpression of TSTD1 mediate poor treatment response in breast cancer

JOURNAL=Frontiers in Oncology

VOLUME=12

YEAR=2022

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.1004261

DOI=10.3389/fonc.2022.1004261

ISSN=2234-943X

ABSTRACT=<p>Epigenetic alterations play a pivotal role in cancer treatment outcomes. Using the methylation array data and The Cancer Genome Atlas (TCGA) dataset, we observed the hypomethylation and upregulation of thiosulfate sulfurtransferase–like domain containing 1 (<italic>TSTD1</italic>) in patients with breast cancer. We examined paired tissues from Taiwanese patients and observed that 65.09% and 68.25% of patients exhibited <italic>TSTD1</italic> hypomethylation and overexpression, respectively. A significant correlation was found between <italic>TSTD1</italic> hypomethylation and overexpression in Taiwanese (74.2%, <italic>p = 0.040</italic>) and Western (88.0%, <italic>p &lt; 0.001</italic>) cohorts. High expression of TSTD1 protein was observed in 68.8% of Taiwanese and Korean breast cancer patients. Overexpression of <italic>TSTD1</italic> in tumors of breast cancer patients was significantly associated with poor 5-year overall survival (<italic>p</italic> = 0.021) and poor chemotherapy response (<italic>p</italic> = 0.008). T47D cells treated with <italic>TSTD1</italic> siRNA exhibited lower proliferation than the control group, and transfection of <italic>TSTD1</italic> in MDA-MB-231 induced the growth of MDA-MB-231 cells compared to the vector control. Additionally, overexpression of <italic>TSTD1</italic> in MCF7 cells mediated a poor response to chemotherapy by epirubicin (<italic>p</italic> &lt; 0.001) and docetaxel (<italic>p</italic> &lt; 0.001) and hormone therapy by tamoxifen (<italic>p</italic> =0.025). Circulating cell-free hypomethylated <italic>TSTD1</italic> was detected in plasma of Taiwanese breast cancer patients with disease progression and poor chemotherapy efficacy. Our results indicate that promoter hypomethylation and overexpression of <italic>TSTD1</italic> in patients with breast cancer are potential biomarkers for poor 5-year overall survival and poor treatment response.</p>