Verification of ferroptosis and pyroptosis and identification of PTGS2 as the hub gene in human coronary artery atherosclerosis

Zhou, Yaqing; Zhou, Hongliang; Liu, Hua; Hou, Can; Jia, Qiaowei; Chen, Jiaxin; Zhang, Sheng; Wang, Yanjun; He, Shu; Jia, En-Zhi

doi:10.1016/j.freeradbiomed.2021.05.009

Cited by 153 publications

(102 citation statements)

References 38 publications

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“…We obtained 33 pyroptosis-related genes from prior studies ( Karki and Kanneganti, 2019 ; Liu D. et al, 2021 ; Ye et al, 2021 ; Zhou et al, 2021 ), and they are presented in Supplementary Table 2 . Consensus Clustering, an unsupervised clustering method, is a common cancer subtype classification method in which the clustering framework incorporates results from multiple runs of an inner-loop clustering algorithm on sub-sampled subjects ( Wilkerson and Hayes, 2010 ; Seymour et al, 2019 ).…”

Section: Methodsmentioning

confidence: 99%

Identification and Validation of the Pyroptosis-Related Molecular Subtypes of Lung Adenocarcinoma by Bioinformatics and Machine Learning

Liu

Zhao

et al. 2021

Front. Cell Dev. Biol.

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Lung cancer remains the leading cause of cancer death globally, with lung adenocarcinoma (LUAD) being its most prevalent subtype. Due to the heterogeneity of LUAD, patients given the same treatment regimen may have different responses and clinical outcomes. Therefore, identifying new subtypes of LUAD is important for predicting prognosis and providing personalized treatment for patients. Pyroptosis-related genes play an essential role in anticancer, but there is limited research investigating pyroptosis in LUAD. In this study, 33 pyroptosis gene expression profiles and clinical information were collected from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. By bioinformatics and machine learning analyses, we identified novel subtypes of LUAD based on 10 pyroptosis-related genes and further validated them in the GEO dataset, with machine learning models performing up to an AUC of 1 for classifying in GEO. A web-based tool was established for clinicians to use our clustering model (http://www.aimedicallab.com/tool/aiml-subphe-luad.html). LUAD patients were clustered into 3 subtypes (A, B, and C), and survival analysis showed that B had the best survival outcome and C had the worst survival outcome. The relationships between pyroptosis gene expression and clinical characteristics were further analyzed in the three molecular subtypes. Immune profiling revealed significant differences in immune cell infiltration among the three molecular subtypes. GO enrichment and KEGG pathway analyses were performed based on the differential genes of the three subtypes, indicating that differentially expressed genes (DEGs) were involved in multiple cellular and biological functions, including RNA catabolic process, mRNA catabolic process, and pathways of neurodegeneration-multiple diseases. Finally, we developed an 8-gene prognostic model that accurately predicted 1-, 3-, and 5-year overall survival. In conclusion, pyroptosis-related genes may play a critical role in LUAD, and provide new insights into the underlying mechanisms of LUAD.

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Section: Methodsmentioning

confidence: 99%

Identification and Validation of the Pyroptosis-Related Molecular Subtypes of Lung Adenocarcinoma by Bioinformatics and Machine Learning

Liu

Zhao

et al. 2021

Front. Cell Dev. Biol.

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“…Ferroptosis was induced by excessive iron and lethal lipid peroxidation (Bai et al, 2020;Stockwell et al, 2020;Zhou et al, 2021). Excessive iron accelerated the production of ROS, which led to lipid peroxidation via Fenton reaction, which is necessary for ferroptosis (Pratt et al, 2011;Dev and Babitt, 2017;Stockwell et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

Construction of a Novel Ferroptosis-Related Gene Signature of Atherosclerosis

Huang

Wang

et al. 2022

Front. Cell Dev. Biol.

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Atheroclerosis refers to a chronic inflammatory disease featured by the accumulation of fibrofatty lesions in the intima of arteries. Cardiovasular events associated with atherosclerosis remain the major causes of mortality worldwide. Recent studies have indicated that ferroptosis, a novel programmed cell death, might participate in the process of atherosclerosis. However, the ferroptosis landscape is still not clear. In this study, 59 genes associated with ferroptosis were ultimately identified in atherosclerosis in the intima. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed for functional annotation. Through the construction of protein–protein interaction (PPI) network, five hub genes (TP53, MAPK1, STAT3, HMOX1, and PTGS2) were then validated histologically. The competing endogenous RNA (ceRNA) network of hub genes was ultimately constructed to explore the regulatory mechanism between lncRNAs, miRNAs, and hub genes. The findings provide more insights into the ferroptosis landscape and, potentially, the therapeutic targets of atherosclerosis.

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“…The severity of AS was associated with Ptgs2 and ACSL4 positively and GPX4 negatively. They concluded that ferroptosis and pyroptosis may regulate the occurrence and progress of AS, providing potential target for the prevention and therapy of coronary artery atherosclerosis (113).…”

Section: Ferroptosis and Atherosclerosismentioning

confidence: 99%

The Link Between Ferroptosis and Cardiovascular Diseases: A Novel Target for Treatment

Chen

Jing

et al. 2021

Front. Cardiovasc. Med.

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Ferroptosis is an iron-dependent cell death, which is characterized by iron overload and lipid peroxidation. Ferroptosis is distinct from apoptosis, necroptosis, autophagy, and other types of cell death in morphology and function. Ferroptosis is regulated by a variety of factors and controlled by several mechanisms, including mitochondrial activity and metabolism of iron, lipid, and amino acids. Accumulating evidence shows that ferroptosis is closely related to a majority of cardiovascular diseases (CVDs), including cardiomyopathy, myocardial infarction, ischemia/reperfusion injury, heart failure, and atherosclerosis. This review summarizes the current status of ferroptosis and discusses ferroptosis as a potential therapeutic target for CVDs.

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Verification of ferroptosis and pyroptosis and identification of PTGS2 as the hub gene in human coronary artery atherosclerosis

Cited by 153 publications

References 38 publications

Identification and Validation of the Pyroptosis-Related Molecular Subtypes of Lung Adenocarcinoma by Bioinformatics and Machine Learning

Identification and Validation of the Pyroptosis-Related Molecular Subtypes of Lung Adenocarcinoma by Bioinformatics and Machine Learning

Construction of a Novel Ferroptosis-Related Gene Signature of Atherosclerosis

The Link Between Ferroptosis and Cardiovascular Diseases: A Novel Target for Treatment

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