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. 2022 Jan 4;21:11. doi: 10.1186/s12943-021-01466-9

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© The Author(s) 2021

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

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Fig. 5 — Comprehensive metabolomics and RNA-seq analyses identify PSTK as a mediator of ferroptosis resistance. A KEGG enrichment analyses of genes differentially expressed following PSTK knockout. B Heatmaps demonstrating gene hits in the ferroptosis gene set. C Gene Set Enrichment Analysis demonstrating that ferroptosis-related genes were significantly enriched following PSTK knockout. D The mRNA expression levels of key ferroptosis-related genes in PSTK-KO and control cells. *p<0.05; Student’s t-test. E KEGG enrichment analysis of differentially abundant metabolites identified in negative ion mode. F KEGG enrichment analysis of differentially abundant metabolites identified in positive ion mode. G-H Volcano plots demonstrating altered metabolite levels. Metabolites associated with GSH metabolism and folate biosynthesis were significantly downregulated, while oxidized phospholipids were significantly upregulated