Comprehensive analysis of the role of SFXN family in breast cancer

Abstract The sideroflexin (SFXN) family is a group of mitochondrial membrane proteins. Although the function of the SFXN family in mitochondria has been widely recognized, the expression levels, role, and prognostic value of this family in breast cancer (BC) have not been clearly articulated and systematically analysed. In our research, SFXN1 and SFXN2 were significantly upregulated in BC versus normal samples based on Gene Expression Profiling Interactive Analysis 2 and the Human Protein Atlas databases. We found that high SFXN1 expression was significantly related to poor prognosis in BC patients and that high SFXN2 expression was significantly associated with good prognosis in BC patients. Gene Ontology analysis of the SFXN family was performed based on the STRING database to explore the potential functions of this family, including biological processes, cellular components, and molecular functions. Based on the MethSurv database, we found that two SFXN1 CpG sites (5′-UTR-S_Shelf-cg06573254 and TSS200-Island-cg17647431), two SFXN2 CpG sites (3′-UTR-Open_Sea-cg04774043 and Body-Open_Sea-cg18994254), one SFXN3 CpG site (Body-S_Shelf-cg17858697), and nine SFXN5 CpG sites (1stExon;5′-UTR-Island-cg03856450, Body-Open_Sea-cg04016113, Body-Open_Sea-cg04197631, Body-Open_Sea-cg07558704, Body-Open_Sea-cg08383863, Body-Open_Sea-cg10040131, Body-Open_Sea-cg10588340, Body-Open_Sea-cg17046766, and Body-Open_Sea-cg22830638) were significantly related to the prognosis of BC patients. According to the ENCORI database, four negative regulatory miRNAs for SFXN1 (hsa-miR-22-3p, hsa-miR-140-5p, hsa-miR-532-5p, and hsa-miR-582-3p) and four negative regulatory miRNAs for SFXN2 (hsa-miR-9-5p, hsa-miR-34a-5p, hsa-miR-532-5p, and hsa-miR-885-5p) were related to poor prognosis for BC patients. This study suggests that SFXN1 and SFXN2 are valuable biomarkers and treatment targets for patients with BC.