A new piRNA-based biomarker for the HER۲ status in breast cancer

Background and Aim: Breast cancer is the most common leading cause of cancer deaths in women worldwide. It is classified into four molecular subgroups based on the presence of estrogen and progesterone hormone receptors and human epidermal growth factor receptors. Each subtype manifests different prognosis, aggression and response to available therapies. Trastuzumab, an anti-HER۲ antibody, is used for breast cancer treatment in patients with HER۲ overexpression or gene amplification. Since this drug is specific to one subtype of breast cancer, determining the subtype is critical in disease management. Current methods for detecting the HER۲ amplification status are not completely efficient so it seems that introducing a new method is necessary. Small non-coding RNAs are stable and detectable in biological fluids, thus they can be good biomarker candidates. Therefore, the first step of our study was to search for small ncRNAs within the region that co-amplified with HER۲.Methods: In this study, we first performed bioinformatics analysis for the expression of a piRNA within the HER۲ (which we called HerPir) in three miRSeq datasets (GSE۶۸۰۸۵, GSE۵۶۱۳۴ and E-MTAB-۴۵۳۹). To confirm bioinformatics results, HER۲ positive and negative breast cancer tumour specimens were collected. RNA was extracted and probed using HerPir probe and the HerPir concentration was assessed.Results: The results of miRSeq datasets analysis demonstrated a significant difference in the level of HerPir between positive and negative HER۲ samples and its expression elevated in HER۲+ and IHC+۳ samples. The results of HerPir expression analysis in tissue samples also confirm these results and indicate a very significant difference of HerPir level with P-value < ۰.۰۰۰۱ between HER۲ positive and negative samples.Conclusion: To evaluate the ability of this piRNA to identify HER۲ status of tumours as a sensitive biomarker, ROC curve was plotted. Based on the bioinformatics and experimental results and area under the ROC curve (AUC) which was ۱, it can be claimed that HerPir can be an accurate and sensitive biomarker to determine HER۲ status of tumours.

Keywords:

Breast cancer , HER۲ status , Biomarker , HerPir