Identification and validation of a ferroptosis‐related gene signature for predicting survival in skin cutaneous melanoma

Abstract Purpose Ferroptosis plays a crucial role in the initiation and progression of melanoma. This study developed a robust signature with ferroptosis‐related genes (FRGs) and assessed the ability of this signature to predict OS in patients with skin cutaneous melanoma (SKCM). Methods RNA‐sequenc...

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Main Authors: Shuai Ping, Siyuan Wang, Yingsong Zhao, Jinbing He, Guanglei Li, Dinglin Li, Zhuo Wei, Jianghai Chen
Format: Article
Language:English
Published: Wiley 2022-09-01
Series:Cancer Medicine
Subjects:
Online Access:https://doi.org/10.1002/cam4.4706
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author Shuai Ping
Siyuan Wang
Yingsong Zhao
Jinbing He
Guanglei Li
Dinglin Li
Zhuo Wei
Jianghai Chen
author_facet Shuai Ping
Siyuan Wang
Yingsong Zhao
Jinbing He
Guanglei Li
Dinglin Li
Zhuo Wei
Jianghai Chen
author_sort Shuai Ping
collection DOAJ
description Abstract Purpose Ferroptosis plays a crucial role in the initiation and progression of melanoma. This study developed a robust signature with ferroptosis‐related genes (FRGs) and assessed the ability of this signature to predict OS in patients with skin cutaneous melanoma (SKCM). Methods RNA‐sequencing data and clinical information of melanoma patients were extracted from TCGA, GEO, and GTEx. Univariate, multivariate, and LASSO regression analyses were conducted to identify the gene signature. A 10 FRG signature was an independent and strong predictor of survival. The predictive performance was assessed using ROC curve. The functions of this gene signature were assessed by GO and KEGG analysis. The statuses of low‐risk and high‐risk groups according to the gene signature were compared by GSEA. In addition, we investigated the possible relationship of FRGs with immunotherapy efficacy. Results A prognostic signature with 10 FRGs (CYBB, IFNG, FBXW7, ARNTL, PROM2, GPX2, JDP2, SLC7A5, TUBE1, and HAMP) was identified by Cox regression analysis. This signature had a higher prediction efficiency than clinicopathological features (AUC = 0.70). The enrichment analyses of DEGs indicated that ferroptosis‐related immune pathways were largely enriched. Furthermore, GSEA showed that ferroptosis was associated with immunosuppression in the high‐risk group. Finally, immune checkpoints such as PDCD‐1 (PD‐1), CTLA4, CD274 (PD‐L1), and LAG3 were also differential expression in two risk groups. Conclusions The 10 FRGs signature were a strong predictor of OS in SKCM and could be used to predict therapeutic targets for melanoma.
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spelling doaj.art-6c46cb2129d3488baf61090bbe183aa12022-12-22T04:30:56ZengWileyCancer Medicine2045-76342022-09-0111183529354110.1002/cam4.4706Identification and validation of a ferroptosis‐related gene signature for predicting survival in skin cutaneous melanomaShuai Ping0Siyuan Wang1Yingsong Zhao2Jinbing He3Guanglei Li4Dinglin Li5Zhuo Wei6Jianghai Chen7Department of Orthopaedics, Liyuan Hospital, Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaDepartment of Orthopaedics, Liyuan Hospital, Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaDepartment of Orthopaedics, Liyuan Hospital, Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaDepartment of Orthopaedics, Liyuan Hospital, Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaDepartment of Orthopaedics, Liyuan Hospital, Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaDepartment of Integrated Traditional Chinese and Western Medicine, Liyuan Hospital Tongji Medical College of Huazhong University of Science and Technology Wuhan ChinaDepartment of Orthopaedics, Liyuan Hospital, Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaDepartment of Hand Surgery, Union Hospital, Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaAbstract Purpose Ferroptosis plays a crucial role in the initiation and progression of melanoma. This study developed a robust signature with ferroptosis‐related genes (FRGs) and assessed the ability of this signature to predict OS in patients with skin cutaneous melanoma (SKCM). Methods RNA‐sequencing data and clinical information of melanoma patients were extracted from TCGA, GEO, and GTEx. Univariate, multivariate, and LASSO regression analyses were conducted to identify the gene signature. A 10 FRG signature was an independent and strong predictor of survival. The predictive performance was assessed using ROC curve. The functions of this gene signature were assessed by GO and KEGG analysis. The statuses of low‐risk and high‐risk groups according to the gene signature were compared by GSEA. In addition, we investigated the possible relationship of FRGs with immunotherapy efficacy. Results A prognostic signature with 10 FRGs (CYBB, IFNG, FBXW7, ARNTL, PROM2, GPX2, JDP2, SLC7A5, TUBE1, and HAMP) was identified by Cox regression analysis. This signature had a higher prediction efficiency than clinicopathological features (AUC = 0.70). The enrichment analyses of DEGs indicated that ferroptosis‐related immune pathways were largely enriched. Furthermore, GSEA showed that ferroptosis was associated with immunosuppression in the high‐risk group. Finally, immune checkpoints such as PDCD‐1 (PD‐1), CTLA4, CD274 (PD‐L1), and LAG3 were also differential expression in two risk groups. Conclusions The 10 FRGs signature were a strong predictor of OS in SKCM and could be used to predict therapeutic targets for melanoma.https://doi.org/10.1002/cam4.4706ferroptosisgene signaturemelanomaoverall survivaltumor immunity
spellingShingle Shuai Ping
Siyuan Wang
Yingsong Zhao
Jinbing He
Guanglei Li
Dinglin Li
Zhuo Wei
Jianghai Chen
Identification and validation of a ferroptosis‐related gene signature for predicting survival in skin cutaneous melanoma
Cancer Medicine
ferroptosis
gene signature
melanoma
overall survival
tumor immunity
title Identification and validation of a ferroptosis‐related gene signature for predicting survival in skin cutaneous melanoma
title_full Identification and validation of a ferroptosis‐related gene signature for predicting survival in skin cutaneous melanoma
title_fullStr Identification and validation of a ferroptosis‐related gene signature for predicting survival in skin cutaneous melanoma
title_full_unstemmed Identification and validation of a ferroptosis‐related gene signature for predicting survival in skin cutaneous melanoma
title_short Identification and validation of a ferroptosis‐related gene signature for predicting survival in skin cutaneous melanoma
title_sort identification and validation of a ferroptosis related gene signature for predicting survival in skin cutaneous melanoma
topic ferroptosis
gene signature
melanoma
overall survival
tumor immunity
url https://doi.org/10.1002/cam4.4706
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