Outstanding prognostic value of novel ferroptosis-related genes in chemoresistance osteosarcoma patients

Zhao, Jiazheng; Zhao, Yi; Ma, Xiaowei; Feng, Helin; Jia, Litao

doi:10.1038/s41598-022-09080-5

Cited by 13 publications

(14 citation statements)

References 42 publications

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“…The overexpression of BAMBI promotes the growth and invasion of human osteosarcoma cells ( 55 ). CBS has a significant correlation to the OS prognosis and is evidenced as an independent prognostic factor ( 56 ). The comprehensive effect of ICD regulated by these genes in OS was reported for the first time in this study.…”

Section: Discussionmentioning

confidence: 99%

Integration of single-cell RNA sequencing and bulk RNA sequencing to reveal an immunogenic cell death-related 5-gene panel as a prognostic model for osteosarcoma

et al. 2022

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BackgroundDespite the comparatively low prevalence of osteosarcoma (OS) compared to other cancer types, metastatic OS has a poor overall survival rate of fewer than 30%. Accumulating data has shown the crucial functions of immunogenic cell death (ICD) in various cancers; nevertheless, the relationship between ICD and OS was not previously well understood. This research aims to determine the function of ICD in OS and construct an ICD-based prognostic panel.MethodsSingle cell RNA sequencing data from GSE162454 dataset distinguished malignant cells from normal cells in OS. The discrepancy in ICD scores and corresponding gene expression was intensively explored between malignant cells and normal cells. Using the RNA sequencing data of the TARGET-OS, GSE16091, GSE21257, and GSE39058 datasets, the molecular subtype of OS was determined by clustering seventeen ICD-related genes obtained from the literature. Differentially expressed genes (DEGs) between different molecular subtypes were identified to develop a novel ICD-associated prognostic panel.ResultsThe malignant cells had a remarkable decrease in the ICD scores and corresponding gene expression compared with normal cells. A total of 212 OS patients were successfully stratified into two subtypes: C1 and C2. C1-like OS patients were characterized by better prognostic outcomes, overexpression of ICD genes, activation of the ICD pathway, high inflitration abundance of immunocytes, and low expression levels of immune checkpoint genes (ICGs); however, the reverse is true in C2-like OS patients. Utilizing the limma programme in R, the DEGs between two subtypes were determined, and a 5-gene risk panel consisting of BAMBI, TMCC2, NOX4, DKK1, and CBS was developed through LASSO-Cox regression analysis. The internal- and external-verification cohorts were employed to verify the efficacy and precision of the risk panel. The AUC values of ROC curves indicated excellent prognostic prediction values of our risk panel.ConclusionsOverall, ICD represented a protective factor against OS, and our 5-gene risk panel serving as a biomarker could effectively evaluate the prognostic risk in patients with OS.

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Section: Discussionmentioning

confidence: 99%

Integration of single-cell RNA sequencing and bulk RNA sequencing to reveal an immunogenic cell death-related 5-gene panel as a prognostic model for osteosarcoma

et al. 2022

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“…A number of studies have analyzed differentially expressed genes and long non-coding RNAs (lncRNAs) during ferroptosis in OS through bioinformatics, and finally identified 26 genes associated with OS prognosis ( 69 – 73 ) (CBS, EGFR, COCS1, PTN, PGD, ZEP36, DLL1, EOMES, ERCC2, G6PD, MYC, SLC39A8, etc.) and 8 lncRNAs ( 74 , 75 ) (RPARP-AS1, PARD6G-AS1, GAS5, UNC5B -AS1, LINC01060, AC124798.1, AC090559.1, and AC104825.1), which created a new prognostic model for OS patients.…”

Section: Research Progress On Ferroptosis In Osteosarcomamentioning

confidence: 99%

Ferroptosis in osteosarcoma: A promising future

Liu

Wang

et al. 2022

Front. Oncol.

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The incidence of osteosarcoma (OS) is increasing year by year, and the prognosis of patients with advanced OS is extremely poor due to the tendency of recurrence and chemotherapy resistance after surgery. Ferroptosis is a novel form of programmed cell death (PCD) that kills cells through iron-dependent lipid peroxidation. Current studies have shown that ferroptosis is closely related to OS and could reduce chemotherapy resistance to a certain extent, which has great therapeutic potential. In this paper, we review the regulatory mechanism of ferroptosis and its research progress in OS, hoping to provide new help for the clinical treatment of OS.

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“…discovered that ferroptosis impacts tumor immunity and it can help to improve the efficacy of patients’ immunotherapy ( 15 ); Zhao et al. revealed that gene regulators of ferroptosis play an essential role in osteosarcoma chemoresistance ( 16 ); He et al. constructed a ferroptosis score model and revealed the therapeutic liability of ferroptosis in melanoma ( 17 ); and Wu et al.…”

Section: Introductionmentioning

confidence: 99%

FerrDb V2: update of the manually curated database of ferroptosis regulators and ferroptosis-disease associations

Zhou

Yuan

et al. 2022

Nucleic Acids Research

152

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Ferroptosis is a mode of regulated cell death characterized by iron-dependent accumulation of lipid peroxidation. It is closely linked to the pathophysiological processes in many diseases. Since our publication of the first ferroptosis database in 2020 (FerrDb V1), many new findings have been published. To keep up with the rapid progress in ferroptosis research and to provide timely and high-quality data, here we present the successor, FerrDb V2. It contains 1001 ferroptosis regulators and 143 ferroptosis-disease associations manually curated from 3288 articles. Specifically, there are 621 gene regulators, of which 264 are drivers, 238 are suppressors, 9 are markers, and 110 are unclassified genes; and there are 380 substance regulators, with 201 inducers and 179 inhibitors. Compared to FerrDb V1, curated articles increase by >300%, ferroptosis regulators increase by 175%, and ferroptosis-disease associations increase by 50.5%. Circular RNA and pseudogene are novel regulators in FerrDb V2, and the percentage of non-coding RNA increases from 7.3% to 13.6%. External gene-related data were integrated, enabling thought-provoking and gene-oriented analysis in FerrDb V2. In conclusion, FerrDb V2 will help to acquire deeper insights into ferroptosis. FerrDb V2 is freely accessible at http://www.zhounan.org/ferrdb/.

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Outstanding prognostic value of novel ferroptosis-related genes in chemoresistance osteosarcoma patients

Cited by 13 publications

References 42 publications

Integration of single-cell RNA sequencing and bulk RNA sequencing to reveal an immunogenic cell death-related 5-gene panel as a prognostic model for osteosarcoma

Integration of single-cell RNA sequencing and bulk RNA sequencing to reveal an immunogenic cell death-related 5-gene panel as a prognostic model for osteosarcoma

Ferroptosis in osteosarcoma: A promising future

FerrDb V2: update of the manually curated database of ferroptosis regulators and ferroptosis-disease associations

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