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Identifying a Ferroptosis-Related Gene Signature for Predicting Biochemical Recurrence of Prostate Cancer

Ferroptosis induced by lipid peroxidation is closely related to cancer biology. Prostate cancer (PCa) is not only a malignant tumor but also a lipid metabolic disease. Previous studies have identified ferroptosis as an important pathophysiological pathway in PCa development and treatment, but its ro...

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Autores principales: Lv, Zhengtong, Wang, Jianlong, Wang, Xuan, Mo, Miao, Tang, Guyu, Xu, Haozhe, Wang, Jianye, Li, Yuan, Liu, Ming
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8586218/
https://www.ncbi.nlm.nih.gov/pubmed/34778244
http://dx.doi.org/10.3389/fcell.2021.666025
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author Lv, Zhengtong
Wang, Jianlong
Wang, Xuan
Mo, Miao
Tang, Guyu
Xu, Haozhe
Wang, Jianye
Li, Yuan
Liu, Ming
author_facet Lv, Zhengtong
Wang, Jianlong
Wang, Xuan
Mo, Miao
Tang, Guyu
Xu, Haozhe
Wang, Jianye
Li, Yuan
Liu, Ming
author_sort Lv, Zhengtong
collection PubMed
description Ferroptosis induced by lipid peroxidation is closely related to cancer biology. Prostate cancer (PCa) is not only a malignant tumor but also a lipid metabolic disease. Previous studies have identified ferroptosis as an important pathophysiological pathway in PCa development and treatment, but its role in the prognosis of PCa is less well known. In this study, we constructed a nine-ferroptosis-related gene risk model that demonstrated strong prognostic and therapeutic predictive power. The higher risk score calculated by the model was significantly associated with a higher ferroptosis potential index, higher Ki67 expression, higher immune infiltration, higher probability of biochemical recurrence, worse clinicopathological characteristics, and worse response to chemotherapy and antiandrogen therapy in PCa. The mechanisms identified by the gene set enrichment analysis suggested that this signature can accurately distinguish high- and low-risk populations, which is possibly closely related to variations in steroid hormone secretion, regulation of endocrine processes, positive regulation of humoral immune response, and androgen response. Results of this study were confirmed in two independent PCa cohorts, namely, The Cancer Genome Atlas cohort and the MSK-IMPACT Clinical Sequencing Cohort, which contributed to the body of scientific evidence for the prediction of biochemical recurrence in patients with PCa. In addition, as the main components of this signature, the effects of the AIFM2 and NFS1 genes on ferroptosis were evaluated and verified by in vivo and in vitro experiments, respectively. The above findings provided new insights and presented potential clinical applications of ferroptosis in PCa.
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spelling pubmed-85862182021-11-13 Identifying a Ferroptosis-Related Gene Signature for Predicting Biochemical Recurrence of Prostate Cancer Lv, Zhengtong Wang, Jianlong Wang, Xuan Mo, Miao Tang, Guyu Xu, Haozhe Wang, Jianye Li, Yuan Liu, Ming Front Cell Dev Biol Cell and Developmental Biology Ferroptosis induced by lipid peroxidation is closely related to cancer biology. Prostate cancer (PCa) is not only a malignant tumor but also a lipid metabolic disease. Previous studies have identified ferroptosis as an important pathophysiological pathway in PCa development and treatment, but its role in the prognosis of PCa is less well known. In this study, we constructed a nine-ferroptosis-related gene risk model that demonstrated strong prognostic and therapeutic predictive power. The higher risk score calculated by the model was significantly associated with a higher ferroptosis potential index, higher Ki67 expression, higher immune infiltration, higher probability of biochemical recurrence, worse clinicopathological characteristics, and worse response to chemotherapy and antiandrogen therapy in PCa. The mechanisms identified by the gene set enrichment analysis suggested that this signature can accurately distinguish high- and low-risk populations, which is possibly closely related to variations in steroid hormone secretion, regulation of endocrine processes, positive regulation of humoral immune response, and androgen response. Results of this study were confirmed in two independent PCa cohorts, namely, The Cancer Genome Atlas cohort and the MSK-IMPACT Clinical Sequencing Cohort, which contributed to the body of scientific evidence for the prediction of biochemical recurrence in patients with PCa. In addition, as the main components of this signature, the effects of the AIFM2 and NFS1 genes on ferroptosis were evaluated and verified by in vivo and in vitro experiments, respectively. The above findings provided new insights and presented potential clinical applications of ferroptosis in PCa. Frontiers Media S.A. 2021-10-29 /pmc/articles/PMC8586218/ /pubmed/34778244 http://dx.doi.org/10.3389/fcell.2021.666025 Text en Copyright © 2021 Lv, Wang, Wang, Mo, Tang, Xu, Wang, Li and Liu. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Lv, Zhengtong
Wang, Jianlong
Wang, Xuan
Mo, Miao
Tang, Guyu
Xu, Haozhe
Wang, Jianye
Li, Yuan
Liu, Ming
Identifying a Ferroptosis-Related Gene Signature for Predicting Biochemical Recurrence of Prostate Cancer
title Identifying a Ferroptosis-Related Gene Signature for Predicting Biochemical Recurrence of Prostate Cancer
title_full Identifying a Ferroptosis-Related Gene Signature for Predicting Biochemical Recurrence of Prostate Cancer
title_fullStr Identifying a Ferroptosis-Related Gene Signature for Predicting Biochemical Recurrence of Prostate Cancer
title_full_unstemmed Identifying a Ferroptosis-Related Gene Signature for Predicting Biochemical Recurrence of Prostate Cancer
title_short Identifying a Ferroptosis-Related Gene Signature for Predicting Biochemical Recurrence of Prostate Cancer
title_sort identifying a ferroptosis-related gene signature for predicting biochemical recurrence of prostate cancer
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8586218/
https://www.ncbi.nlm.nih.gov/pubmed/34778244
http://dx.doi.org/10.3389/fcell.2021.666025
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