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pmid:35903347
Comprehensive Analysis of the Aberrance and Functional Significance of Ferroptosis in Gastric Cancer.
Jun Xiao · Lingyan Zheng · Jingfeng Liu
Frontiers in pharmacology · 2022 doi:10.3389/fphar.2022.919490
Paper
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Experiment
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Data
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Analysis
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Complete file
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Methods: We gathered five GC cohorts, namely, TCGA-STAD, GSE84437, GSE62254, GSE26901, and GSE15459. Unsupervised clustering analysis was adopted to cluster GC patients into different ferroptosis subtypes based on ferroptosis regulators. Immune cell infiltration and hallmark pathway activity were estimated via ssGSEA. The ferroptosis index was developed with the PCA computational method. Response to chemotherapy agents and small molecular compounds was inferred via GDSC, CTRP, and PRISM projects. Two anti-PD-1 therapy cohorts were gathered and the potential of FPI in predicting immune response was assessed. Results: Expression profiles, genetic mutations, DNA methylation, prognostic implications, and drug sensitivity of ferroptosis regulators were characterized in GC. Three ferroptosis subtypes were clustered with distinct prognosis, hallmark pathway activity, and tumor-infiltrating immune cells. Ferroptosis levels were quantified based on the expression of prognostic ferroptosis-related signatures. The significant relationships between FPI and clinicopathological characteristics were observed. Furthermore, high FPI was in relation to poor prognosis, inflamed tumor microenvironment (TME) as well as high sensitivity to chemotherapy agents (docetaxel and cisplatin), and CTRP- and PRISM-derived compounds. Also, FPI acted as a promising predictor of immune response. 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