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Association between miRNA signatures in serum samples from epidermal growth factor inhibitor treated patients and
Sarah Kemski1,2, Vivien Molitor1, Michael Steffens1
1Research Division, Federal Institute for Drugs and Medical Devices (BfArM), Bonn, Germany.
Objective:
Epidermal growth factor receptor inhibitors (EGFRI) are used as targeted cancer therapy. On average 70% of patients treated with EGFRIs suffer from skin toxicity. Studies showed a correlation between overall survival and the appearance of a skin rash, which is used as a biomarker for therapy efficacy. Micro RNAs (miRNA) as tumor or resistance biomarkers for cancer therapy are also highly investigated. In our study, we searched for associations of miRNA expression profiles in serum, with the severity of skin rash, in order to identify tentative therapy predictive biomarkers.
Materials And Methods:
Five candidate miRNAs were selected, based on an earlier in vitro next-generation-sequencing-experiment and after literature search. MiR-21, miR-31, miR-17, miR-106b and miR-520e were investigated in serum samples from patients (n = 254) treated with EGFRI. The quantitative expression of miRNA was tested for association with the occurrence/severity of the rash.
Results:
In our cohort of patients treated with EGFR inhibiting monoclonal antibodies, miR-21 and miR-520e serum concentrations were negatively correlated with severity of skin rash (p-value 0.000582 and 1.53e-07 linear-trend-test) whereas for miR-31, a positive correlation was observed (p-value 9.01e-06 linear-trend-test).
Conclusions:
This suggests that miR-21, miR-31 and miR-520e expression might be a treatment dependent marker for EGFRI induced skin rash.
Insights
Serum microRNAs (miRNAs) like miR-21, miR-31, and miR-520e may predict epidermal growth factor receptor inhibitor (EGRI) skin toxicity. These miRNAs could serve as biomarkers for treatment response and managing side effects in cancer patients.
Area of Science:
- Oncology
- Dermatology
- Molecular Biology
Background:
- Epidermal growth factor receptor inhibitors (EGFRIs) are crucial targeted cancer therapies.
- Skin toxicity affects ~70% of patients on EGFRIs, with rash severity correlating to survival.
- MicroRNAs (miRNAs) are investigated as potential biomarkers for cancer therapy efficacy and resistance.
Purpose of the Study:
- To investigate associations between serum miRNA expression profiles and the severity of skin rash in patients treated with EGFRIs.
- To identify potential predictive biomarkers for EGFRI-induced skin toxicity.
Main Methods:
- Five candidate miRNAs (miR-21, miR-31, miR-17, miR-106b, miR-520e) were selected based on prior in vitro experiments and literature review.
- Quantitative expression of these miRNAs was analyzed in serum samples from 254 patients treated with EGFRIs.
- Statistical tests were used to assess the correlation between miRNA expression levels and rash occurrence/severity.
Main Results:
- Serum concentrations of miR-21 and miR-520e showed a negative correlation with skin rash severity (p < 0.0006 and p < 1.6e-07, respectively).
- Serum miR-31 concentration demonstrated a positive correlation with skin rash severity (p < 9.1e-06).
Conclusions:
- miR-21, miR-31, and miR-520e serum expression levels may serve as treatment-dependent biomarkers.
- These findings suggest potential for using these miRNAs to predict or monitor EGFRI-induced skin rash.
