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Updated: Mar 19, 2026
Exploring Caspase Mutations and Post-Translational Modification by Molecular Modeling Approaches
Published on: October 13, 2022
Transcript expression and genetic variability analysis of caspases in breast carcinomas suggests CASP9 as the most
Background:
Apoptosis plays a critical role in cancer cell survival and tumor development. We provide a hypothesis-generating screen for further research by exploring the expression profile and genetic variability of caspases (2, 3, 7, 8, 9, and 10) in breast carcinoma patients. This study addressed isoform-specific caspase transcript expression and genetic variability in regulatory sequences of caspases 2 and 9.
Methods:
Gene expression profiling was performed by quantitative real-time PCR in tumor and paired non-malignant tissues of two independent groups of patients. Genetic variability was determined by high resolution melting, allelic discrimination, and sequencing analysis in tumor and peripheral blood lymphocyte DNA of the patients.
Results:
CASP3 A+B and S isoforms were over-expressed in tumors of both patient groups. The CASP9 transcript was down-regulated in tumors of both groups of patients and significantly associated with expression of hormonal receptors and with the presence of rs4645978-rs2020903-rs4646034 haplotype in the CASP9 gene. Patients with a low intratumoral CASP9A/B isoform expression ratio (predicted to shift equilibrium towards anti-apoptotic isoform) subsequently treated with adjuvant chemotherapy had a significantly shorter disease-free survival than those with the high ratio (p=0.04). Inheritance of CC genotype of rs2020903 in CASP9 was associated with progesterone receptor expression in tumors (p=0.003).
Conclusions:
Genetic variability in CASP9 and expression of its splicing variants present targets for further study.
Insights
Altered expression of CASP3 and CASP9 (caspase) genes in breast cancer impacts patient survival. Genetic variations in CASP9 and its splicing variants offer potential therapeutic targets for breast carcinoma.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Apoptosis is crucial for cancer cell survival and tumor progression.
- Investigated caspase (caspase 2, 3, 7, 8, 9, and 10) expression and genetic variability in breast carcinoma.
- Focused on isoform-specific caspase transcript expression and genetic variations in regulatory sequences of caspases 2 and 9.
Purpose of the Study:
- To explore the expression profile and genetic variability of caspases in breast carcinoma patients.
- To investigate the relationship between caspase expression, genetic variability, and clinical outcomes.
- To identify potential therapeutic targets based on caspase gene alterations.
Main Methods:
- Gene expression profiling using quantitative real-time PCR in tumor and non-malignant tissues.
- High-resolution melting, allelic discrimination, and sequencing for genetic variability analysis in tumor and peripheral blood lymphocyte DNA.
- Analysis of two independent patient cohorts.
Main Results:
- CASP3 isoforms (A+B and S) were over-expressed in tumors.
- CASP9 transcript was down-regulated in tumors, associated with hormonal receptor expression and a specific CASP9 haplotype (rs4645978-rs2020903-rs4646034).
- A low CASP9A/B isoform ratio correlated with shorter disease-free survival in patients receiving adjuvant chemotherapy; rs2020903 CC genotype was linked to progesterone receptor expression.
Conclusions:
- Genetic variability in the CASP9 gene is associated with breast cancer characteristics.
- Expression of CASP9 splicing variants presents potential targets for further investigation.
- Altered caspase expression and genetic makeup may influence breast cancer progression and treatment response.
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