Integrative bioinformatics analysis reveals miR-494 and its target genes as predictive biomarkers of trastuzumab-resistant breast cancer

• Main Authors: Adam Hermawan, Herwandhani Putri
• Format: Article
• Language: English
• Published: SpringerOpen 2020-04-01
• Series: Journal of the Egyptian National Cancer Institute
• Subjects: miR-494; Chemoresistance; Trastuzumab; Bioinformatics; Predictive biomarker
• Online Access: http://link.springer.com/article/10.1186/s43046-020-00028-2

Abstract Background The focus of trastuzumab resistance biomarkers in recent decades has been on epigenetic and non-coding RNA-based mechanisms. In this study, the potential of miR-494 and its target genes as predictive biomarkers for breast cancer (BC) resistance to trastuzumab was identified. The microarray data were obtained from the GEO database, including GSE101841, GSE75669, and GSE66305. Data processing was conducted using GEO2R to obtain differentially expressed genes (DEGs). Results The data analysis using GEO2R revealed that DEGs from GSE101841 and GSE75669 consisted of 3 and 135 upregulated miRNAs, respectively. On the other hand, the same analysis revealed 8 and 226 downregulated miRNAs for DEGs from GSE101841 and GSE75669, respectively. A Venn diagram showed that one miR was detectable in serum and tissue samples, namely miR-494. The miR-494 target was predicted using the miRecords database and resulted in 69 target genes. A Venn diagram between miR-494 target genes from miRecords and the mRNA array from GSE66305 revealed three potential targets of CNR1, RBM39, and ZNF207. A Kaplan–Meier survival plot showed that BC patients with a high miR-494 level and a low ZNF207 mRNA level had significantly worse overall survival. Validation of target genes in BC samples and trastuzumab-resistant and -sensitive BC cells with GEPIA and ONCOMINE highlighted the potential of CNR1, RBM39, and ZNF207 as predictive biomarkers of trastuzumab resistance in BC cells. Conclusion Taken together, these results suggest that miR-494 plays a role in the mechanism of BC resistance to trastuzumab by involving its target genes CNR1, RBM39, and ZNF207.