AUTHOR=Wang Quanqiang , Zhao Misheng , Zhang Tianyu , Zhang Bingxin , Zheng Ziwei , Lin Zhili , Zhou Shujuan , Zheng Dong , Chen Zixing , Zheng Sisi , Zhang Yu , Lin Xuanru , Dong Rujiao , Chen Jingjing , Qian Honglan , Hu Xudong , Zhuang Yan , Zhang Qianying , Jiang Songfu , Ma Yongyong 

TITLE=Comprehensive analysis of ferroptosis-related genes in immune infiltration and prognosis in multiple myeloma

JOURNAL=Frontiers in Pharmacology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2023.1203125

DOI=10.3389/fphar.2023.1203125

ISSN=1663-9812

ABSTRACT=<p><bold>Background:</bold> One particular type of cellular death that is known as ferroptosis is caused by the excessive lipid peroxidation. It is a regulated form of cell death that can affect the response of the tumor cells. Currently, it is not known if the presence of this condition can affect the prognosis of patients with multiple myeloma (MM).</p><p><bold>Methods:</bold> In this study, we studied the expression differences and prognostic value of ferroptosis-related genes (FRGs) in MM, and established a ferroptosis risk scoring model. In order to improve the prediction accuracy and clinical applicability, a nomogram was also established. Through gene enrichment analysis, pathways closely related to high-risk groups were identified. We then explored the differences in risk stratification in drug sensitivity and immune patterns, and evaluated their value in prognostic prediction and treatment response. Lastly, we gathered MM cell lines and samples from patients to confirm the expression of marker FRGs using quantitative real-time PCR (qRT-PCR).</p><p><bold>Results:</bold> The ability to predict the survival of MM patients is a challenging issue. Through the use of a risk model derived from ferroptosis, we were able to develop a more accurate prediction of the disease’s prognosis. They were then validated by a statistical analysis, which showed that the model is an independent factor in the prognosis of MM. Patients of high ferroptosis risk scores had a much worse chance of survival than those in the low-risk groups. The calibration and power of the nomogram were also strong. We noted that the link between the ferroptosis risk score and the clinical treatment was suggested by the FRG’s significant correlation with the immune checkpoint genes and the medication sensitivity. We validated the predictive model using qRT-PCR.</p><p><bold>Conclusion:</bold> We demonstrated the association between FRGs and MM, and developed a new risk model for prognosis in MM patients. Our study sheds light on the potential clinical relevance of ferroptosis in MM and highlights its potential as a therapeutic target for patients with this disease.</p>