Promoter hypomethylation associated with elevated TRIM33 expression in triple-negative breast cancer patients

Introduction Triple-negative breast cancer (TNBC) is a highly aggressive and diverse subtype of breast cancer with few therapeutic choices and poor prognosis. This is mostly because of recurrence, metastasis, and therapeutic resistance. Members of the tripartite motif-containing protein family (TRIM) have emerged as significant regulators of tumor growth due to their functions in cell proliferation, invasion, migration, and metastasis. TRIM33 has been shown to operate context-dependently as either a tumor suppressor or a tumor promoter in various cancers, partly because of its participation in TGF-β-related signaling pathways. However, little is known about the expression pattern and epigenetic regulation of TRIM33 in TNBC, especially in Indian patients. Methods Twenty-eight patients with histologically confirmed TNBC were included in the study. Tumor tissue and paired adjacent non-tumor breast tissue were collected at the time of surgery. TRIM33 mRNA and protein expression were evaluated using quantitative real-time PCR (qRT-PCR), western blotting, and immunohistochemistry. TRIM33 promoter methylation status was assessed using methylation-specific PCR (MS-PCR). Results TRIM33 expression was increased in TNBC tissue compared with paired adjacent non-tumor tissue. Increased TRIM33 mRNA expression was observed in 19 of 28 cases (67.9%), while elevated TRIM33 protein expression was detected in 16 of 28 cases (57.1%). An unmethylated/hypomethylated TRIM33 promoter pattern was observed in 22 of 28 cases (78.6%).TRIM33 protein expression showed significant associations with selected clinicopathological characteristics, including clinical stage. Promoter methylation status was also associated with selected clinicopathological parameters. Conclusion Promoter hypomethylation of TRIM33 was frequently observed in TNBC and was associated with increased TRIM33 expression and selected clinicopathological characteristics. These findings suggest a potential role for epigenetic regulation of TRIM33 in TNBC and warrant validation in larger patient cohorts.