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Studying the Stoichiometry of Epidermal Growth Factor Receptor in Intact Cells using Correlative Microscopy
Published on: September 11, 2015
MicroRNA-21 as a predictor and prognostic factor for trastuzumab therapy in human epidermal growth factor receptor
Marwa Badr1, Hebatallah Said1, Manal L Louka1
1Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
Abstract:
Breast cancer is the second most common cancer diagnosed worldwide. Human epidermal growth factor receptor 2 (HER2)-positive breast cancer represents about 20% to 30% of all breast cancers. Trastuzumab is used in the treatment of HER2-positive breast cancer. MicroRNA-21 (miR-21) is an oncomiR that acts by inhibiting many tumor-suppressor genes. We analyzed the relative expression levels of serum miR-21 in 20 HER2-positive metastatic breast cancer patients before and after 3 months of treatment with trastuzumab. miR-21 levels decreased with a high significant difference after trastuzumab therapy (P = 0.001). Although miR-21 expression levels were lower in responders than in nonresponders, the difference was not statistically significant ( P = 0.6). Our results demonstrated a significant negative correlation between its basal expression, expression levels after treatment, and time to progression ( P = 0.03 and 0.01, respectively). These results make miR-21 a potential prognostic factor for HER2-positive metastatic breast cancer patients. Additionally, it can be an interesting potential target in therapy using antisense oligonucleotides for miR-21.
Insights
Serum microRNA-21 (miR-21) levels significantly decreased after trastuzumab treatment in HER2-positive metastatic breast cancer patients. Lower miR-21 levels correlated with longer time to progression, suggesting miR-21 as a potential prognostic factor.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Breast cancer is a prevalent malignancy, with HER2-positive subtypes accounting for 20-30% of cases.
- Trastuzumab is a standard therapy for HER2-positive breast cancer.
- MicroRNA-21 (miR-21) is an oncomiR implicated in tumor progression by suppressing tumor-suppressor genes.
Purpose of the Study:
- To investigate the change in serum miR-21 levels in HER2-positive metastatic breast cancer patients treated with trastuzumab.
- To evaluate the correlation between miR-21 expression and treatment response or time to progression.
Main Methods:
- Serum samples were collected from 20 HER2-positive metastatic breast cancer patients before and after 3 months of trastuzumab therapy.
- Relative expression levels of miR-21 were quantified.
- Statistical analysis was performed to assess changes in miR-21 levels and correlations with clinical outcomes.
Main Results:
- Serum miR-21 levels showed a statistically significant decrease (P=0.001) after trastuzumab treatment.
- While responders tended to have lower miR-21 levels than non-responders, this difference was not statistically significant (P=0.6).
- A significant negative correlation was observed between basal and post-treatment miR-21 levels and time to progression (P=0.03 and P=0.01, respectively).
Conclusions:
- Serum miR-21 levels significantly decrease following trastuzumab therapy in HER2-positive metastatic breast cancer.
- miR-21 may serve as a potential prognostic biomarker for HER2-positive metastatic breast cancer.
- miR-21 inhibition using antisense oligonucleotides could be a potential therapeutic strategy.
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