331P - miR-21 and miR-34a as biomarkers of radiotherapy skin adverse events in ductal carcinoma in situ

Background

Ductal carcinoma in situ (DCIS) is a non-invasive type of breast cancer treated with surgery and adjuvant radiotherapy (RT). RT improves local disease control, but also causes adverse effects. Molecular factors could contribute to interindividual variability in the incidence of skin adverse events after RT. Radiation exposure can affect expression of miRNAs, small non-coding RNAs involved in post-transcriptional regulation of gene expression. Our aim was to evaluate whether miR-21 and miR-34a expression changes after RT and if miRNA expression is associated with skin adverse events of RT in patients with DCIS.

Methods

Our prospective study included 119 patients with DCIS treated with adjuvant RT. Skin adverse events were assessed using Common Terminology Criteria for Adverse Events (CTCAE) v.5 immediately after RT and six months after RT. MiRNA was isolated from plasma before and after RT and quantitative PCR was used to determine miR-21 and miR-34a expression. Non-parametric tests and logistic regression were used in statistical analysis.

Results

Immediately after RT, 5.7% patients had grade 2 skin adverse events, while 26.1% patients experienced grade 2 adverse events after six months. More skin adverse events after six months were observed in smokers (p=0.036). After RT, the expression of miR-21 (p=0.001) and miR-34a (p<0.001) was significantly increased. Patients with a greater increase in miR-34a expression after RT were more likely to have a higher grade of skin adverse events immediately after RT, even after adjustment for clinical parameters (OR_adj=1.13; 95% CI_adj=1.02-1.26; p_adj=0.026). Similarly, greater increase in miR-34a expression was associated with more adverse events six months after RT, but the association was only significant adjustment for clinical parameters (OR_adj=1.13; 95% CI_adj=1.01-1.27; p_adj=0.035). Expression of miR-21 was not associated with skin adverse events.

Conclusions

Our results suggest that miR-21 and miR-34a expression increases after RT and miR-34a expression might serve as a biomarker of RT skin adverse events. Research grants: ARRS J3-1753, ARRS J3-2527, P1-0170 and P3-0321.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Slovenian Research Agency.

Disclosure

All authors have declared no conflicts of interest.