FOXO4 May Be a Biomarker of Postmenopausal Osteoporosis

Abstract

Purpose Postmenopausal osteoporosis (PMOP) is a common and debilitating chronic disease, but it has just no cure options. The objective of this study was to identify genes associated with osteoporosis and reveal potential therapeutic targets. Methods Expression profiles from GSE13850 and GSE56815 datasets were combined for differential expression analysis. Extraction of intersecting genes from the combined datasets and the differentially expressed genes in GSE56814 were performed to construct a multi-scale embedded gene co-expression network analysis (MEGENA) to obtain module genes. Module genes with an area under the receiver operating characteristic curve (AUC) >0.60 were chosen to construct the least absolute shrinkage and selection operator (LASSO) model to obtain feature genes. A regulated network was constructed using differentially expressed micro-RNAs (miRNAs) in GSE74209 and feature genes. Finally, key genetic pathways and pathways of the Kyoto Encyclopedia of Genes and Genomes were identified and explored. Results The commonly identified differentially expressed genes involve oxidative phosphorylation and caffeine metabolism. We identified 66 modules with 2354 module genes based on MEGENA. CARD8, FOXO4, IL1R2, MPHOSPH6, MPRIP, MYOM1, PRR5L and YIPF4 were identified as feature genes by the LASSO model. Furthermore, predicted miRNA target genes included 8 genes associated with PMOP. The largest AUC was observed for FOXO4, which was found at the nexus of feature genes and miRNA-regulated genes and which correlated with the upregulation of dendritic cells. Moreover, FOXO4 was found to be involved in ABC transporters, as well as cocaine and nicotine addiction. Conclusion FOXO4 may serve as potential biomarker and therapeutic target for PMOP.

FoxO4 mediates macrophage M2 polarization by promoting LXA4R expression in an ovalbumin-induced allergic asthma model in mice

“…40 FOXO4 is upregulated and may act as a biomarker of postmenopausal osteoporosis. 41 Inhibition of FoxO4 dampens hippocampal neuronal apoptosis, which participates in the protective role of sevoflurane against intracerebral hemorrhage. 42 The decreased mRNA expression is shown in a vasculitis model via the tumor necrosis factor-α (TNF-α) stimulation of primary human coronary artery endothelial cells (HCAECs), in which FoxO4 stabilizes endothelial cell homeostasis.…”

Discovery of novel serum biomarkers for diagnosing and predicting postmenopausal osteoporosis patients by 4D‐label free protein omics

“…Numerous biomarkers for PMOP had been explored and identified based on various pathogenic mechanisms of PMOP. Inflammation and the adaptive immune system had been investigated as one of the most important mechanisms 6,7 . Hong Fang et al found that the high systemic immune‐inflammation index (SII) was a high‐risk factor for POPM, indicating that the SII can not only be applied as a diagnostic biomarker but also be utilized to predict the risk of fracture incidence 8 .…”

“…Inflammation and the adaptive immune system had been investigated as one of the most important mechanisms. 6,7 Hong Fang et al found that the high systemic immune-inflammation index (SII) was a high-risk factor for POPM, indicating that the SII can not only be applied as a diagnostic biomarker but also be utilized to predict the risk of fracture incidence. 8 The increasing peripheral level of inflammatory-related molecules was found to be associated with the occurrence and severity of PMOP.…”