Evaluation of the expression level of MFAP4, miR-582-5p, and miR-1181 in tumor and marginal tissues of patients with breast cancer

Abstract

The role of medical in BC can be divided into two distinct eras: pre- and post-classification of patients based on hormone receptors. This classification not only advanced researchers' understanding of the disease's pathology but also improved prognosis and reduced chemotherapy challenges by introducing hormone therapy as a new treatment approach. This progress was performed by microarray analysis and the identification of patient expression profiles. The primary aim of this research is to discover novel candidate biomarkers from gene and miRNA microarray datasets and further evaluate them using qPCR. Methods: Initially, we chose three gene datasets (GSE139038, GSE24124, and GSE9309) and two miRNA datasets (GSE45666 and GSE42072) GEO database. After analyzing the gene datasets in the RStudio environment, we utilized the g:Profiler database to identify cellular pathways and components. Notably, ECM participated in most significant components and pathways. Consequently, the Microfibrillar-Associated Protein 4 (MFAP4) gene emerged as a novel candidate biomarker for BC. Additionally, by scrutinizing both miRNA datasets and miRWalk results, we discovered miR-1181 and miR-582-5p as two novel miRNAs capable of targeting MFAP4. We also examined MFAP4, miR-1181, and miR-582-5p using UALCAN, a program that visualizes the results from TCGA data. Finally, we conducted qPCR analysis on a total of 50 tumor tissues and 50 adjacent tumor tissues in order to corroborate our in silico findings. Results: According to in silico findings, the qPCR revealed the downregulation of MFAP4 and the upregulation of miR-1181 and miR-582-5p. However, there was no considerable association obsereved between MFAP4 and either of the two miRNAs. Furthermore, the ROC curve demonstrated the importance of their combination in diagnostic tests. However, the reliability of the sensitivity and specificity of each factor remained doubtful. Finally, the role of MFAP4, miR-1181, and miR-582-5p in BC prognosis was predicted by KMP findings.