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The mRNA expression of SATB1 and SATB2 in human breast cancer
Neill Patani1, Wen Jiang, Robert Mansel
1Department of Breast Surgery, St, George's University of London, London, UK. neillpatani@hotmail.com
Background:
SATB1 is a nuclear protein that has been recently reported to be a 'genome organizer' which delineates specific epigenetic modifications at target gene loci, directly up-regulating metastasis-associated genes while down-regulating tumor-suppressor genes. In this study, the level of mRNA expression of SATB1 and SATB2 were assessed in normal and malignant breast tissue in a cohort of women with breast cancer and correlated to conventional clinico-pathological parameters.
Materials And Methods:
Breast cancer tissues (n = 115) and normal background tissues (n = 31) were collected immediately after excision during surgery. Following RNA extraction, reverse transcription was carried out and transcript levels were determined using real-time quantitative PCR and normalized against beta-actin expression. Transcript levels within the breast cancer specimens were compared to the normal background tissues and analyzed against TNM stage, nodal involvement, tumour grade and clinical outcome over a 10 year follow-up period.
Results:
The levels of SATB1 were higher in malignant compared with normal breast tissue (p = 0.0167). SATB1 expression increased with increasing TNM stage (TNM1 vs. TNM2 p = 0.0264), increasing tumour grade (grade1 vs. grade 3 p = 0.017; grade 2 vs. grade 3 p = 0.0437; grade 1 vs. grade 2&3 p = 0.021) and Nottingham Prognostic Index (NPI) (NPI-1 vs. NPI-3 p = 0.0614; NPI-2 vs. NPI-3 p = 0.0495). Transcript levels were associated with oestrogen receptor (ER) positivity (ER(-) vs. ER(+) p = 0.046). SABT1 expression was also significantly correlated with downstream regulated genes IL-4 and MAF-1 (Pearson's correlation coefficient r = 0.21 and r = 0.162) and SATB2 (r = 0.506). After a median follow up of 10 years, there was a trend for higher SATB1 expression to be associated with shorter overall survival (OS). Higher levels of SATB2 were also found in malignant compared to background tissue (p = 0.049). SATB2 expression increased with increasing tumour grade (grade 1 vs. grade 3 p = 0.035). SATB2 was associated with ER positivity (ER(-) vs. ER(+) p = 0.0283) within ductal carcinomas. Higher transcript levels showed a significant association with poorer OS (p = 0.0433).
Conclusion:
SATB1 mRNA expression is significantly associated with poor prognostic parameters in breast cancer, including increasing tumour grade, TNM stage and NPI. SATB2 mRNA expression is significantly associated with increasing tumour grade and poorer OS. These results are consistent with the notion that SATB1 acts as a 'master genome organizer' in human breast carcinogenesis.
Insights
SATB1 and SATB2 mRNA expression are elevated in breast cancer tissues. Higher levels of SATB1 and SATB2 correlate with poor prognostic indicators and reduced overall survival in breast cancer patients.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- SATB1 functions as a "genome organizer," influencing gene expression by epigenetic modifications.
- SATB1 is known to up-regulate metastasis-associated genes and down-regulate tumor-suppressor genes.
Purpose of the Study:
- To assess the mRNA expression levels of SATB1 and SATB2 in breast cancer.
- To correlate these expression levels with clinico-pathological parameters and patient outcomes.
Main Methods:
- Real-time quantitative PCR was used to determine SATB1 and SATB2 mRNA levels in 115 breast cancer tissues and 31 normal tissues.
- Expression levels were analyzed against TNM stage, tumor grade, Nottingham Prognostic Index (NPI), and estrogen receptor (ER) status.
- Clinical outcomes were followed for 10 years.
Main Results:
- SATB1 and SATB2 mRNA levels were significantly higher in malignant breast tissue compared to normal tissue.
- SATB1 expression correlated with increasing TNM stage, tumor grade, and NPI.
- Both SATB1 and SATB2 expression were associated with estrogen receptor positivity and poorer overall survival.
Conclusions:
- SATB1 mRNA expression is a significant indicator of poor prognosis in breast cancer, linked to advanced tumor stage and grade.
- SATB2 mRNA expression is also associated with increasing tumor grade and poorer overall survival.
- These findings support SATB1's role as a "master genome organizer" in human breast carcinogenesis.