Research Papers:

Association between miRNA signatures in serum samples from epidermal growth factor inhibitor treated patients and skin toxicity

Sarah Kemski, Vivien Molitor, Michael Steffens, Tim J. Nümm, Nadine Herrmann, Thorsten Hornung, Thomas Bieber, Christian Schumann, Volker Kächele, Thomas Seufferlein, Volker Heinemann, Catharina Scholl and Julia Carolin Stingl _

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Oncotarget. 2021; 12:982-995. https://doi.org/10.18632/oncotarget.27953

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Sarah Kemski1,2, Vivien Molitor1, Michael Steffens1, Tim J. Nümm2, Nadine Herrmann2, Thorsten Hornung2, Thomas Bieber2, Christian Schumann3, Volker Kächele4, Thomas Seufferlein5, Volker Heinemann6, Catharina Scholl1 and Julia Carolin Stingl7

1 Research Division, Federal Institute for Drugs and Medical Devices (BfArM), Bonn, Germany

2 Department of Dermatology and Allergy, Christine Kühne Center for Allergy Research and Education (CK-CARE), University Hospital-Bonn, Bonn, Germany

3 Department of Pulmonology, Thorax Oncology, Sleep and Respiration Medicine, Hospital Group Allgäu, Kempten, Germany

4 Medical Centre for Haematology and Oncology, Ulm, Germany

5 Department of Internal Medicine I, University of Ulm, Ulm, Germany

6 Department of Internal Medicine III, Ludwig-Maximilians-University of Munich, Munich, Germany

7 Institute of Clinical Pharmacology, University Hospital of the RWTH Aachen, Aachen, Germany

Correspondence to:

Julia Carolin Stingl,email: [email protected]

Keywords: miRNA; EGFR; EGFRI; cancer; skin toxicity

Received: November 09, 2020     Accepted: April 19, 2021     Published: May 11, 2021

Copyright: © 2021 Kemski et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


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.

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