Construction of a Ferroptosis-Related Gene Signature for Predicting Survival and Immune Microenvironment in Melanoma Patients

Ni Zeng; Liwen Ma; Yuxin Cheng; Qingyue Xia; Yueyue Li; Yihe Chen; Zhiyu Lu; Qian Lu; Feng Jiang; Dan Luo

doi:10.2147/IJGM.S327348

Construction of a Ferroptosis-Related Gene Signature for Predicting Survival and Immune Microenvironment in Melanoma Patients

Int J Gen Med. 2021 Oct 5:14:6423-6438. doi: 10.2147/IJGM.S327348. eCollection 2021.

Authors

Ni Zeng^{1

2}, Liwen Ma³, Yuxin Cheng¹, Qingyue Xia¹, Yueyue Li¹, Yihe Chen¹, Zhiyu Lu¹, Qian Lu¹, Feng Jiang⁴, Dan Luo¹

Affiliations

¹ Department of Dermatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210000, People's Republic of China.
² Department of Dermatology, Affiliated Hospital of Zunyi Medical University, Zunyi, 563000, People's Republic of China.
³ Department of Dermatology, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, 210000, People's Republic of China.
⁴ Department of Neonatology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, 200011, People's Republic of China.

Abstract

Objective: In this research, we studied the genes associated with ferroptosis to develop a prognostic model and find out an association with tumor immune microenvironment in skin cutaneous melanoma (SKCM) patients.

Methods: To find SKCM-related ferroptosis genes, we used Cox regression and LASSO approach on 60 genes related to ferroptosis and SKCM-related RNA-seq. Following that, a ferroptosis-related gene signature was created. Time-dependent ROC curve and Kaplan-Meier analysis were calculated to determine its capability of prediction. Besides, several assessments were used to evaluate overall survival (OS), accompanied by the creation of a nomogram for the clinicopathologic factors and the ferroptosis-related gene signature we established. We also investigated the relationship between ferroptosis-related gene signature with three immune checkpoints and immune cell infiltration.

Results: Our prognostic model included two genes (ALOX5, CHAC1). In both TCGA and GEO cohorts, OS was lower in high-risk category. Using our gene signature, we can reliably predict OS. Additionally, our gene signature can predict immune cell infiltration and SKCM immunotherapy response.

Conclusion: Our gene signature has shown to be a reliable predictor of OS, reflect the immune microenvironment, and predict the effectiveness of immunotherapy for SKCM patients.

Keywords: SKCM; ferroptosis; immune checkpoint; immune microenvironment; skin cutaneous melanoma.