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

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

doi:10.3389/fphar.2023.1203125

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

Front Pharmacol. 2023 Aug 7:14:1203125. doi: 10.3389/fphar.2023.1203125. eCollection 2023.

Authors

Quanqiang Wang¹, Misheng Zhao², Tianyu Zhang¹, Bingxin Zhang¹, Ziwei Zheng¹, Zhili Lin¹, Shujuan Zhou¹, Dong Zheng¹, Zixing Chen³, Sisi Zheng¹, Yu Zhang¹, Xuanru Lin¹, Rujiao Dong¹, Jingjing Chen¹, Honglan Qian¹, Xudong Hu¹, Yan Zhuang¹, Qianying Zhang¹, Songfu Jiang¹, Yongyong Ma^{1

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Affiliations

¹ Department of Hematology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
² Department of Clinical Laboratory, Wenzhou People's Hospital, Wenzhou, China.
³ Department of Hepatobiliary Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
⁴ Key Laboratory of Intelligent Treatment and Life Support for Critical Diseases of Zhejiang Province, Wenzhou, Zhejiang, China.
⁵ Zhejiang Engineering Research Center for Hospital Emergency and Process Digitization, Wenzhou, Zhejiang, China.

Abstract

Background: 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). Methods: 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). Results: 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. Conclusion: 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.

Keywords: drug sensitivity; ferroptosis; gene set enrichment analysis; immune analysis; multiple myeloma; overall survival; prognostic marker genes.

Grants and funding

This study was supported by grants from The National Natural Science Foundation (grant no. 82270212), the Natural Science Foundation of Zhejiang province (grant no. LY20H080003) and the Wenzhou Municipal Science and Technology Bureau (grant no. Y20220716).