301P - Epigenetic modifications of IL-17 gene in patients with early breast cancer and healthy controls

Background

During malignant transformation, the composition and expression of cell surface molecules are changing allowing recognition by the host immune system. Interleukin 17 (IL-17) is an inflammatory mediator involved in all phases of the inflammatory process and tumour development and progression. The aim of this study was to determine the IL-17 gene methylation level and IL-17 serum concentration in patients with different surrogate subtypes of early breast cancer (eBC) and healthy controls (HCs).

Methods

Peripheral blood samples were obtained from a consecutive series of 130 female patients treated at the University Hospital Centre (UHC) Zagreb, Croatia, and 30 female HCs. The level of methylation of four CpG dinucleotide loci (CPG1, CPG2, CPG3, CPG4) in the promoter region of the IL-17 gene was measured by pyrosequencing with prior bisulfite conversion, while serum IL-17 concentrations were determined by enzyme-linked immunosorbent assay (ELISA). Blood samples, clinical and histopathological data were collected with prior UHC Zagreb 02/21 AG Institutional Review Board approval.

Results

According to the Mann-Whitney test, the HCs methylation level of the promotor region of the IL-17 gene differed significantly from the BC patients (p = 0.0011), together with the methylation level of four individual CpG loci, also (p values; CPG1 0.0067; CPG2 0.0018; CPG3 CPG 0.0029; CPG4 0.0032, respectively). There was a statistically significant difference according to the Kruskal-Wallis test in CPG3 locus methylation among BC surrogate subtypes (p=0.010), whereas no difference in the methylation of the other three loci was observed. Preoperative IL-17 serum concentration was significantly higher in patients with HER-2 enriched and triple-negative eBC (Kruskal-Wallis test, p=0.022).

Conclusions

This study confirmed differences in epigenetic modification of IL-17 gene in women with eBC compared to HCs. Differences in the IL-17 gene methylation and IL-17 serum concentration in patients with different subtypes of BC were observed. Further research is planned to define the impact of IL-17 on eBC outcome in this cohort.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Research was funded by the grants from University of Zagreb for financial support to research groups 2019 and 2020.

Disclosure

All authors have declared no conflicts of interest.