ARG2, MAP4K5 and TSTA3 as Diagnostic Markers of Steroid-Induced Osteonecrosis of the Femoral Head and Their Correlation With Immune Infiltration

Rongguo Yu; Jiayu Zhang; Youguang Zhuo; Xu Hong; Jie Ye; Susu Tang; Nannan Liu; Yiyuan Zhang

doi:10.3389/fgene.2021.691465

ARG2, MAP4K5 and TSTA3 as Diagnostic Markers of Steroid-Induced Osteonecrosis of the Femoral Head and Their Correlation With Immune Infiltration

Front Genet. 2021 Jul 26:12:691465. doi: 10.3389/fgene.2021.691465. eCollection 2021.

Authors

Rongguo Yu^{1

2}, Jiayu Zhang³, Youguang Zhuo², Xu Hong², Jie Ye², Susu Tang², Nannan Liu², Yiyuan Zhang^{1

4}

Affiliations

¹ Department of Orthopaedics, Fuzhou Second Affiliated Hospital, Xiamen University, Xiamen, China.
² Fuzhou Second Affiliated Hospital, Xiamen University, Xiamen, China.
³ School of Clinical Medicine, Yunnan University of Traditional Chinese Medicine, Kunming, China.
⁴ Fuzhou Second Hospital Affiliated to Xiamen University, Fujian, China.

Abstract

Background: The diagnosis for steroid-induced osteonecrosis of the femoral head (SONFH) is hard to achieve at the early stage, which results in patients receiving ineffective treatment options and a poor prognosis for most cases. The present study aimed to find potential diagnostic markers of SONFH and analyze the effect exerted by infiltration of immune cells in this pathology.

Materials and methods: R software was adopted for identifying differentially expressed genes (DEGs) and conducting functional investigation based on the microarray dataset. Then we combined SVM-RFE, WGCNA, LASSO logistic regression, and random forest (RF) algorithms for screening the diagnostic markers of SONFH and further verification by qRT-PCR. The diagnostic values were assessed through receiver operating characteristic (ROC) curves. CIBERSORT was then adopted for assessing the infiltration of immune cells and the relationship of infiltration-related immune cells and diagnostic markers.

Results: We identified 383 DEGs overall. This study found ARG2, MAP4K5, and TSTA3 (AUC = 0.980) to be diagnostic markers of SONFH. The results of qRT-PCR showed a statistically significant difference in all markers. Analysis of infiltration of immune cells indicated that neutrophils, activated dendritic cells and memory B cells were likely to show the relationship with SONFH occurrence and progress. Additionally, all diagnostic markers had different degrees of correlation with T cell follicular helper, neutrophils, memory B cells, and activated dendritic cells.

Conclusion: ARG2, MAP4K5, and TSTA3 are potential diagnostic genes for SONFH, and infiltration of immune cells may critically impact SONFH occurrence and progression.

Keywords: biomarker; diagnostic marker; gene expression omnibus; immune cells; steroid-induced osteonecrosis of the femoral head.