Identification and Validation of a Prognostic Signature for Prostate Cancer Based on Ferroptosis-Related Genes

Liu, Huan; Gao, Lei; Xie, Tongxin; Li, Jie; Zhai, Ting‐Shuai; Xu, Yunfei

doi:10.3389/fonc.2021.623313

Cited by 34 publications

(31 citation statements)

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“…5 C). Researchers have studied prognosis models of PCa with modification conditions such as ferroptosis, m6A, and immune score, such as seven-gene signature discovered by Liu et al [ 25 ], eleven-gene signature discovered by Zhang et al [ 26 ], and seven-gene signature discovered by Lv et al [ 27 ]. Through comparison, we found that the accuracy of our risk signature was superior to other prognostic models according to AUC values of the ROC curve (Fig.…”

Section: Resultsmentioning

confidence: 99%

A novel defined risk signature based on pyroptosis-related genes can predict the prognosis of prostate cancer

Cao

Tong

et al. 2022

BMC Med Genomics

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Background Pyroptosis can not only inhibit the occurrence and development of tumors but also develop a microenvironment conducive to cancer growth. However, pyroptosis research in prostate cancer (PCa) has rarely been reported. Methods The expression profile and corresponding clinical data were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Patients were divided into different clusters using consensus clustering analysis, and differential genes were obtained. We developed and validated a prognostic biomarker for biochemical recurrence (BCR) of PCa using univariate Cox analysis, Lasso-Cox analysis, Kaplan–Meier (K–M) survival analysis, and time-dependent receiver operating characteristics (ROC) curves. Results The expression levels of most pyroptosis-related genes (PRGs) are different not only between normal and tumor tissues but also between different clusters. Cluster 2 patients have a better prognosis than cluster 1 patients, and there are significant differences in immune cell content and biological pathway between them. Based on the classification of different clusters, we constructed an eight genes signature that can independently predict the progression-free survival (PFS) rate of a patient, and this signature was validated using a GEO data set (GSE70769). Finally, we established a nomogram model with good accuracy. Conclusions In this study, PRGs were used as the starting point and based on the expression profile and clinical data, a prognostic signature with a high predictive value for biochemical recurrence (BCR) following radical prostatectomy (RP) was finally constructed, and the relationship between pyroptosis, immune microenvironment, and PCa was explored, providing important clues for future research on pyroptosis and immunity.

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Section: Resultsmentioning

confidence: 99%

A novel defined risk signature based on pyroptosis-related genes can predict the prognosis of prostate cancer

Cao

Tong

et al. 2022

BMC Med Genomics

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“…However, further research found that this signature has no obvious independent prognostic value on the overall survival rate of patients (Figure S6). Researchers have studied prognosis models of PCa with modi cation conditions such as ferroptosis, m6A, and immune score, such as seven-gene signature discovered by Liu et al (15), eleven-gene signature discovered by Zhang et al ( 16), and sevengene signature discovered by Lv et al (17). Through comparison, we found that the accuracy of PRGscore signature was superior to other prognostic models (Figure 5D).…”

Section: Construction and Veri Cation Of Prognostic Signature Based On Prg Clustersmentioning

confidence: 73%

“…Finally, PRG-score focuses directly on PCa cell death patterns compared to other models. Researchers have studied prognosis models of PCa with modi cation conditions such as ferroptosis, m6A, and immune score, such as seven-gene signature(15) discovered by Liu et al, eleven-gene signature (16) discovered by Zhang et al, and seven-gene signature (17) discovered by Lv et al Through comparison, we found that the accuracy of PRG-score signature was superior to other prognostic models, and our research focused more on factors that directly contributed to tumor cell death and changed tumor microenvironment. As a result, our model is more valuable for facilitating treatment.In our study, pyroptosis-related genes are used as the starting point, PCa patients are divided into different subtypes, DEGs are identi ed, and a prognosis model is constructed that can accurately predict tumor progression-free survival rate and overall survival rate of patients.…”

mentioning

confidence: 99%

A Novel Defined Pyroptosis-Related Gene Signature For Predicting the Prognosis of Prostate Cancer

Cao

Tong

et al. 2021

Preprint

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Background: Pyroptosis can not only inhibit the occurrence and development of tumors but also develop a microenvironment conducive to cancer growth. However, pyroptosis research in prostate cancer (PCa) has rarely been reported.Methods: The expression profile and corresponding clinical data were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Patients were divided into different clusters using consensus clustering analysis, and differential genes were obtained. We developed and validated a prognostic signature for biochemical recurrence (BCR) of PCa using univariate Cox analysis, LASSO-COX analysis, Kaplan-Meier (K-M) survival analysis, and time-dependent receiver operating characteristics (ROC) curves.Results: The expression levels of most pyroptosis-related genes (PRGs) are different not only between normal and tumor tissues but also between different clusters. Cluster2 patients have a better prognosis than cluster1 patients, and there are significant differences in immune cell content and biological pathway between them. Based on the classification of different clusters, we constructed an eight genes signature that can independently predict the progression-free survival (PFS) rate of a patient, and this signature was validated using a GEO data set (GSE70769). Finally, we established a nomogram model with good usability.Conclusions: In this study, PRGs were used as the starting point and based on the expression profile and clinical data, a prognostic signature with a high predictive value for biochemical recurrence (BCR) following radical prostatectomy (RP) was finally constructed, and the relationship between pyroptosis, immune microenvironment, and PCa was explored, providing important clues for future research on pyroptosis and immunity.

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“…Since a closed association between ferroptosis and urologic malignancies, targeting ferroptosis may be a treatment option for cancer patients. Liu et al [ 123 ] demonstrated that ferroptosis related genes, such as AKR1C3, ALOXE3, ATP5MC3, and CARS1, may serve as the promising prognostic biomarkers and potential drug targets in PCa patients. Yang et al [ 111 ] indicate that ferroptosis inducer erastin is a potential target in treating castration‑resistant PCa patients.…”

Section: Future Perspectives Of Ferroptosis In Urologic Malignanciesmentioning

confidence: 99%

Roles of ferroptosis in urologic malignancies

Zhao

Wu³

et al. 2021

Cancer Cell Int

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Ferroptosis, an iron-dependent form of non-apoptotic cell death, is believed to strongly contribute to the pathogenesis of multiple cancers. Recently, the positive association between ferroptosis and urologic malignancies has drawn considerable attention, while a comprehensive review focused on this issue is absent. Based on this review, ferroptosis has been implicated in the development and therapeutic responses of prostate cancer, kidney cancer, and bladder cancer. Mechanistically, a large number of biomolecules and tumor-associated signaling pathways, including DECR1, PANX2, HSPB1, ACOT8, SUV39H1, NCOA4, PI3K-AKT-mTOR signaling, VHL/HIF-2α pathway, and Hippo/TAZ signaling pathway, have been reported to regulate ferroptosis in urologic cancers. Ferroptosis inducers, such as erastin, ART, CPNPs, and quinazolinyl-arylurea derivatives, exert potential therapeutic effects per se and/or enhance the anticancer response of other anticancer drugs in urologic oncology. A better understanding of ferroptosis may provide a promising way to treat therapy-resistant urologic cancers.

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Identification and Validation of a Prognostic Signature for Prostate Cancer Based on Ferroptosis-Related Genes

Cited by 34 publications

References 50 publications

A novel defined risk signature based on pyroptosis-related genes can predict the prognosis of prostate cancer

A novel defined risk signature based on pyroptosis-related genes can predict the prognosis of prostate cancer

A Novel Defined Pyroptosis-Related Gene Signature For Predicting the Prognosis of Prostate Cancer

Roles of ferroptosis in urologic malignancies

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