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Optimization of a Multiplex RNA-based Expression Assay Using Breast Cancer Archival Material
Published on: August 1, 2018
Expression Profiling of SWI/SNF Complex Subunits in Triple-Negative Breast Cancer Using Tissue Microarray and
Shang Wang1, Chen Gao2, Qi Wang2
1Department of Pathology, School of Basic Medicine, Qingdao University, Qingdao, People's Republic of China.
Introduction:
The SWI/SNF (SWItch/Sucrose Non - Fermentable) complex is a multi - subunit, ATPase - dependent chromatin - remodeling complex involved in regulating key cellular processes. Tumors with SWI/SNF loss tend to be poorly differentiated and aggressive. Triple - negative breast cancer (TNBC) typically has a high histological grade and a poor prognosis. Given the limited reports on the SWI/SNF complex in breast cancer, we focused on its role in TNBC.
Methods:
Using tissue microarray and immunohistochemistry (IHC), we evaluated the expression of four important subunits of the SWI/SNF complex (SMARCB1, SMARCA2, ARID1A, and SMARCA4) in 104 TNBC tissues, which included 96 cases of conventional TNBC and 8 cases of low - grade TNBC. Additionally, we evaluated the endogenous expression of the four subunits in five breast cancer cell lines by real - time quantitative PCR (RT - qPCR). These cell lines consisted of two TNBC cell lines (MDA - MB - 231, MDA - MB - 468) and three non - TNBC cell lines (MCF - 7, T47D, and MDA - MB - 453).
Results:
The IHC results indicated that the deletion rate of SMARCA2 was the highest in TNBC compared with other subunits (91/104, 87.5%) (p < 0.0001), and SMARCA4 had the highest retention rate (98/104, 94.2%). Whether low - grade TNBC was excluded or not, there was no significant difference between the deletion rate and various clinicopathological parameters. Consistently, we found that SMARCA2 exhibited the lowest expression level across all five cell lines (p < 0.01). SMARCA4 showed the highest expression in all cell lines except MDA - MB - 453, in which ARID1A expression was the highest.
Conclusion:
These results indicate that TNBC is characterized by a high proportion of SMARCA2 deletion and positive expression of SMARCA4, which are significant molecular features. The roles and potential mechanisms of these two factors in TNBC require further investigation.
Insights
Triple-negative breast cancer (TNBC) frequently shows SWI/SNF complex alterations, specifically high SMARCA2 deletion and SMARCA4 retention. These molecular features warrant further investigation into their role in TNBC progression.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The SWI/SNF (SWItch/Sucrose Non-Fermentable) complex is crucial for cellular processes and its loss is linked to aggressive tumors.
- Triple-negative breast cancer (TNBC) is characterized by poor prognosis and high histological grade.
- Limited research exists on the SWI/SNF complex's role in TNBC.
Purpose of the Study:
- To investigate the expression patterns of key SWI/SNF subunits in TNBC.
- To identify potential molecular markers associated with TNBC.
Main Methods:
- Tissue microarray and immunohistochemistry (IHC) were used to analyze SWI/SNF subunit expression (SMARCB1, SMARCA2, ARID1A, SMARCA4) in 104 TNBC tissues.
- Real-time quantitative PCR (RT-qPCR) assessed subunit expression in five breast cancer cell lines (two TNBC, three non-TNBC).
Main Results:
- SMARCA2 deletion was observed in 87.5% of TNBC cases, the highest deletion rate among the studied subunits.
- SMARCA4 showed the highest retention rate (94.2%) in TNBC tissues.
- SMARCA2 had the lowest expression in TNBC cell lines, while SMARCA4 was highly expressed, except in MDA-MB-453 where ARID1A was highest.
Conclusions:
- TNBC is molecularly characterized by a high frequency of SMARCA2 deletion and SMARCA4 expression.
- These findings highlight SMARCA2 and SMARCA4 as significant molecular features in TNBC.
- Further research is needed to elucidate the functional roles and mechanisms of SMARCA2 and SMARCA4 in TNBC.
