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

**Authors:** Maria Eduarda R. de Oliveira, Marina P. Silva, Estella F. Silvestri, Samia F. Sanches, Isabella D. R. Trufelli, Ludmila F. B. Fabbrini, Glaucia L. da Veiga, Fernando Luiz A. Fonseca, Beatriz da C. A. Alves

PMC · DOI: 10.3390/ijms27062752 · International Journal of Molecular Sciences · 2026-03-18

## TL;DR

This study explores the expression of tumor suppressor genes REST and RASSF1A in the blood of breast cancer patients, suggesting REST as a potential biomarker for diagnosis and risk assessment.

## Contribution

The study identifies REST as a potential molecular marker in breast cancer through its expression patterns in peripheral blood.

## Key findings

- REST expression was significantly lower in breast cancer patients compared to healthy controls.
- REST expression negatively correlated with BIRADS classification and showed a diagnostic AUC of 0.72.
- RASSF1A was negatively correlated with heparanase levels but did not differentiate patients from controls.

## Abstract

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.

## Linked entities

- **Genes:** RASSF1 (Ras association domain family member 1) [NCBI Gene 11186], REST (RE1 silencing transcription factor) [NCBI Gene 5978]
- **Diseases:** breast cancer (MONDO:0004989)

## Full-text entities

- **Genes:** RASSF1 (Ras association domain family member 1) [NCBI Gene 11186] {aka 123F2, NORE2A, RASSF1A, RDA32, REH3P21}, REST (RE1 silencing transcription factor) [NCBI Gene 5978] {aka DFNA27, GINGF5, HGF5, NRSF, WT6, XBR}, HPSE (heparanase) [NCBI Gene 10855] {aka HPA, HPA1, HPR1, HPSE1, HSE1}
- **Diseases:** metastasis (MESH:D009362), Breast Cancer (MESH:D001943), Tumor (MESH:D009369)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

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## References

52 references — full list in the complete paper: https://tomesphere.com/paper/PMC13026583/full.md

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Source: https://tomesphere.com/paper/PMC13026583