AUTHOR=Yu Rongguo , Zhang Jiayu , Zhuo Youguang , Hong Xu , Ye Jie , Tang Susu , Liu Nannan , Zhang Yiyuan 

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

JOURNAL=Frontiers in Genetics

VOLUME=Volume 12 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2021.691465

DOI=10.3389/fgene.2021.691465

ISSN=1664-8021

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

Material/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 forests (RF) algorithms for screening the diagnostic markers of SONFH and further verify by qRT-PCR. The diagnostic values were assessed through receiver operating characteristic (ROC) curves. Lastly, CIBERSORT was adopted for assessing the infiltration of immune cells and the relationship of infiltration-related immune cells and diagnostic markers. 

Results:
We identified overall 383 DEGs here. 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 was different degrees of correlation with resting NK cells, T cells follicular helper, neutrophils, memory B cells and activated dendritic cells.

Conclusions: 
In conclusion, ARG2, MAP4K5 and TSTA3 were considered as potential diagnostic genes for SONFH, and infiltration of immune cells may critically impact SONFH occurrence and progression.