Int J Mol Sci 2026 Mar 18;276:. doi: 10.3390/ijms27062752.

REST and RASSF1A Tumor Suppressor Genes in Peripheral Blood: Potential Molecular Markers in Breast Cancer.

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Tumor suppressor genes, such as RASSF1A and REST, play a central role in regulating cell proliferation. RASSF1A is frequently inactivated in various cancers, being associated with poor prognosis and metastasis. REST loss promotes the activation of genes related to invasion and estrogen sensitivity. We aimed to evaluate the expression of REST and RASSF1A in peripheral blood of breast cancer patients at different treatment stages and to associate the results with clinical and laboratory variables. Peripheral blood samples from breast cancer patients were collected at diagnosis and at 3 and 6 months after the start of chemotherapy; blood samples from healthy women were also collected. Gene expression was quantified by qPCR and associated with clinical variables. REST expression was significantly lower in patients (p < 0.0001), showing a negative correlation with the BIRADS classification and an AUC of 0.72. RASSF1A showed no significant difference between groups but was negatively correlated with heparanase (r = -0.4213; p < 0.0001). No relevant variations in gene expression were observed among the serial collections, nor associations with histological type. Downregulation of REST expression in the peripheral blood of breast cancer patients suggests its potential as an auxiliary biomarker for diagnosis and risk stratification. RASSF1A was correlated with mechanisms associated with tumor progression but did not differentiate patients from controls.

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