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Ferroptosis Markers Predict the Survival, Immune Infiltration, and Ibrutinib Resistance of Diffuse Large B cell Lymphoma

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Abstract

Diffuse large B cell lymphoma (DLBCL) is the most common hematological malignancy in adults. Ferroptosis is an iron-dependent programmed cell death caused by lipid peroxidation. However, the potential functions of ferroptosis in the DLBCL prognosis, immune infiltration, and drug resistance remain unknown. Data of DLBCL patients were downloaded from public GEO databases and TCGA cohort. R software was used for analysis. Ferroptosis-related risk score model was constructed using LASSO Cox regression analysis. The prognosis of the model and its association with immune cells infiltration and ibrutinib-resistance were studied by single-sample gene set enrichment analysis (ssGSEA) and correlation analysis. Ferroptosis-related risk score model was constructed with 11 ferroptosis-related genes. DLBCL patients can be divided into high- or low-risk groups with this model. High-risk patients had significant shorter survival (p < 0.001). The area under curve at 3-year was 0.779. Functional enrichment analysis was mainly associated with the immune response. High score patients were positively correlated with immunosuppressive cell infiltration, including macrophages and regulatory T cells, and immunoevasion checkpoints, such as CTLA4, PD-L1, LAG-3, and TIM-3. We also found that tumors with high risk would resist to ibrutinib treatment and uncovered that acetaminophen, as a ferroptosis inducer, inhibited the defined high-risk gene expression in the ibrutinib-resistant DLBCL cell lines. Ferroptosis-related risk score model can predict the overall survival (OS) of DLBCL patients and ibrutinib resistance of ABC-DLBCL cells, which was associated with immunosuppression status within the tumor microenvironment.

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Data Availability

The data used to support the findings of this study are available from the corresponding author on reasonable request.

Abbreviations

DLBCL:

Diffuse large B cell lymphoma

GEO:

Gene expression omnibus

TCGA:

The Cancer Genome Atlas

LASSO:

Least absolute shrinkage and selection operator

ssGSEA:

Single-sample gene set enrichment analysis

CTLA4:

Cytotoxic T lymphocyte–associated protein 4

PDL1:

Programmed cell death 1 ligand 1

PD-L1:

Programmed cell death 1

LAG-3:

Lymphocyte activating 3

TIM-3:

Hepatitis A virus cellular receptor 2 (HAVCR2)

2B4:

CD244 molecule

OS:

Overall survival

NHL:

Non-Hodgkin’s lymphoma

ABC:

Activated B cell

GCB:

Germinal center B cell

TME:

Tumor microenvironment

TNBC:

Triple-negative breast cancer

FRGs:

Ferroptosis-related genes

FerrDb:

Ferroptosis database

CTD:

Comparative Toxicogenomics Database

DEGs:

Differentially expressed genes

PFGs:

Prognostic ferroptosis genes

PCA:

Principal component analysis

ROC:

Receiver operating characteristic

GO:

Gene Ontology

KEGG:

Kyoto Encyclopedia of Genes and Genomes

DC:

Activated dendritic cell

Tfh:

T follicular helper cell

APAP:

Acetaminophen

References

  1. Wright, G.W., D.W. Huang, J.D. Phelan, Z.A. Coulibaly, S. Roulland, and R.M. Young. 2020. A probabilistic classification tool for genetic subtypes of diffuse large B cell lymphoma with therapeutic implications. Cancer Cell 37 (4): 551–568. https://doi.org/10.1016/j.ccell.2020.03.015.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Chapuy, B., C. Stewart, A.J. Dunford, J. Kim, A. Kamburov, R.A. Redd, M.S. Lawrence, M. Roemer, A.J. Li, M. Ziepert, A.M. Staiger, J.A. Wala, M.D. Ducar, I. Leshchiner, E. Rheinbay, A. Taylor-Weiner, C.A. Coughlin, J.M. Hess, C.S. Pedamallu, D. Livitz, D. Rosebrock, M. Rosenberg, A.A. Tracy, H. Horn, P. van Hummelen, A.L. Feldman, B.K. Link, A.J. Novak, J.R. Cerhan, T.M. Habermann, R. Siebert, A. Rosenwald, A.R. Thorner, M.L. Meyerson, T.R. Golub, R. Beroukhim, G.G. Wulf, G. Ott, S.J. Rodig, S. Monti, D.S. Neuberg, M. Loeffler, M. Pfreundschuh, L. Trumper, G. Getz, and M.A. Shipp. 2018. Molecular subtypes of diffuse large B cell lymphoma are associated with distinct pathogenic mechanisms and outcomes. Nature Medicine 24 (5): 679–690. https://doi.org/10.1038/s41591-018-0016-8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Xu-Monette, Z.Y., L. Li, J.C. Byrd, K.J. Jabbar, G.C. Manyam, D.W.C. Maria, M. van den Brand, A. Tzankov, C. Visco, J. Wang, K. Dybkaer, A. Chiu, A. Orazi, Y. Zu, G. Bhagat, K.L. Richards, E.D. Hsi, W.W. Choi, J. Huh, M. Ponzoni, A.J. Ferreri, M.B. Moller, B.M. Parsons, J.N. Winter, M. Wang, F.B. Hagemeister, M.A. Piris, V.K.J. Han, L.J. Medeiros, Y. Li, A.B. van Spriel, and K.H. Young. 2016. Assessment of CD37 B-cell antigen and cell of origin significantly improves risk prediction in diffuse large B-cell lymphoma. Blood 128 (26): 3083–3100. https://doi.org/10.1182/blood-2016-05-715094.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Ruppert, A.S., J.G. Dixon, G. Salles, A. Wall, D. Cunningham, V. Poeschel, C. Haioun, H. Tilly, H. Ghesquieres, M. Ziepert, J. Flament, C. Flowers, Q. Shi, and N. Schmitz. 2020. International prognostic indices in diffuse large B-cell lymphoma: A comparison of IPI, R-IPI, and NCCN-IPI. Blood 135 (23): 2041–2048. https://doi.org/10.1182/blood.2019002729.

    Article  CAS  PubMed  Google Scholar 

  5. Bari, A., L. Marcheselli, S. Sacchi, R. Marcheselli, S. Pozzi, P. Ferri, E. Balleari, P. Musto, S. Neri, S.M. Aloe, and M.C. Cox. 2010. Prognostic models for diffuse large B-cell lymphoma in the rituximab era: A never-ending story. Annals of Oncology 21 (7): 1486–1491. https://doi.org/10.1093/annonc/mdp531.

    Article  CAS  PubMed  Google Scholar 

  6. Lenz, G., G. Wright, S.S. Dave, W. Xiao, J. Powell, H. Zhao, W. Xu, B. Tan, N. Goldschmidt, J. Iqbal, J. Vose, M. Bast, K. Fu, D.D. Weisenburger, T.C. Greiner, J.O. Armitage, A. Kyle, L. May, R.D. Gascoyne, J.M. Connors, G. Troen, H. Holte, S. Kvaloy, D. Dierickx, G. Verhoef, J. Delabie, E.B. Smeland, P. Jares, A. Martinez, A. Lopez-Guillermo, E. Montserrat, E. Campo, R.M. Braziel, T.P. Miller, L.M. Rimsza, J.R. Cook, B. Pohlman, J. Sweetenham, R.R. Tubbs, R.I. Fisher, E. Hartmann, A. Rosenwald, G. Ott, H.K. Muller-Hermelink, D. Wrench, T.A. Lister, E.S. Jaffe, W.H. Wilson, W.C. Chan, and L.M. Staudt. 2008. Stromal gene signatures in large-B-cell lymphomas. New England Journal of Medicine 359 (22): 2313–2323. https://doi.org/10.1056/NEJMoa0802885.

    Article  CAS  PubMed  Google Scholar 

  7. Tilly, H., D.S.M. Gomes, U. Vitolo, A. Jack, M. Meignan, A. Lopez-Guillermo, J. Walewski, M. Andre, P.W. Johnson, M. Pfreundschuh, and M. Ladetto. 2015. Diffuse large B-cell lymphoma (DLBCL): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals of Oncology 26 (Suppl 5): v116–v125. https://doi.org/10.1093/annonc/mdv304.

    Article  PubMed  Google Scholar 

  8. Harkins, R.A., A. Chang, S.P. Patel, M.J. Lee, J.S. Goldstein, S. Merdan, C.R. Flowers, and J.L. Koff. 2019. Remaining challenges in predicting patient outcomes for diffuse large B-cell lymphoma. Expert Review of Hematology 12 (11): 959–973. https://doi.org/10.1080/17474086.2019.1660159.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Tam, C.S., J. Trotman, S. Opat, J.A. Burger, G. Cull, D. Gottlieb, R. Harrup, P.B. Johnston, P. Marlton, J. Munoz, J.F. Seymour, D. Simpson, A. Tedeschi, R. Elstrom, Y. Yu, Z. Tang, L. Han, J. Huang, W. Novotny, L. Wang, and A.W. Roberts. 2019. Phase 1 study of the selective BTK inhibitor zanubrutinib in B-cell malignancies and safety and efficacy evaluation in CLL. Blood 134 (11): 851–859. https://doi.org/10.1182/blood.2019001160.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Roschewski, M., L.M. Staudt, and W.H. Wilson. 2014. Diffuse large B-cell lymphoma-treatment approaches in the molecular era. Nature Reviews. Clinical Oncology 11 (1): 12–23. https://doi.org/10.1038/nrclinonc.2013.197.

    Article  CAS  PubMed  Google Scholar 

  11. Younes, A., L.H. Sehn, P. Johnson, P.L. Zinzani, X. Hong, J. Zhu, C. Patti, D. Belada, O. Samoilova, C. Suh, S. Leppa, S. Rai, M. Turgut, W. Jurczak, M.C. Cheung, R. Gurion, S.P. Yeh, A. Lopez-Hernandez, U. Duhrsen, C. Thieblemont, C.S. Chiattone, S. Balasubramanian, J. Carey, G. Liu, S.M. Shreeve, S. Sun, S.H. Zhuang, J. Vermeulen, L.M. Staudt, and W. Wilson. 2019. Randomized phase III trial of ibrutinib and rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone in non-germinal center B-cell diffuse large B-cell lymphoma. Journal of Clinical Oncology 37 (15): 1285–1295. https://doi.org/10.1200/JCO.18.02403.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Wen, T., J. Wang, Y. Shi, H. Qian, and P. Liu. 2021. Inhibitors targeting Bruton’s tyrosine kinase in cancers: Drug development advances. Leukemia 35 (2): 312–332. https://doi.org/10.1038/s41375-020-01072-6.

    Article  CAS  PubMed  Google Scholar 

  13. Mou, Y., J. Wang, J. Wu, D. He, C. Zhang, C. Duan, and B. Li. 2019. Ferroptosis, a new form of cell death: Opportunities and challenges in cancer. Journal of Hematology & Oncology 12 (1): 34. https://doi.org/10.1186/s13045-019-0720-y.

    Article  Google Scholar 

  14. Smedby, K.E., and M. Ponzoni. 2017. The aetiology of B-cell lymphoid malignancies with a focus on chronic inflammation and infections. Journal of Internal Medicine 282 (5): 360–370. https://doi.org/10.1111/joim.12684.

    Article  CAS  PubMed  Google Scholar 

  15. Hong, Z., P. Tang, B. Liu, C. Ran, C. Yuan, Y. Zhang, Y. Lu, X. Duan, Y. Yang, and H. Wu. 2021. Ferroptosis-related genes for overall survival prediction in patients with colorectal cancer can be inhibited by gallic acid. International Journal of Biological Sciences 17 (4): 942–956. https://doi.org/10.7150/ijbs.57164.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Wang, S., C. Wu, D. Ma, and Q. Hu. 2021. Identification of a ferroptosis-related gene signature (FRGS) for predicting clinical outcome in lung adenocarcinoma. PeerJ 9: e11233. https://doi.org/10.7717/peerj.11233.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Wang, W., M. Green, J.E. Choi, M. Gijon, P.D. Kennedy, J.K. Johnson, P. Liao, X. Lang, I. Kryczek, A. Sell, H. Xia, J. Zhou, G. Li, J. Li, W. Li, S. Wei, L. Vatan, H. Zhang, W. Szeliga, W. Gu, R. Liu, T.S. Lawrence, C. Lamb, Y. Tanno, M. Cieslik, E. Stone, G. Georgiou, T.A. Chan, A. Chinnaiyan, and W. Zou. 2019. CD8(+) T cells regulate tumour ferroptosis during cancer immunotherapy. Nature 569 (7755): 270–274. https://doi.org/10.1038/s41586-019-1170-y.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Yu, B., B. Choi, W. Li, and D.H. Kim. 2020. Magnetic field boosted ferroptosis-like cell death and responsive MRI using hybrid vesicles for cancer immunotherapy. Nature Communications 11 (1): 3637. https://doi.org/10.1038/s41467-020-17380-5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Jiang, Z., S.O. Lim, M. Yan, J.L. Hsu, J. Yao, Y. Wei, S.S. Chang, H. Yamaguchi, H.H. Lee, B. Ke, J.M. Hsu, L.C. Chan, G.N. Hortobagyi, L. Yang, C. Lin, D. Yu, and M.C. Hung. 2021. TYRO3 induces anti-PD-1/PD-L1 therapy resistance by limiting innate immunity and tumoral ferroptosis. Journal of Clinical Investigation 131(8). https://doi.org/10.1172/JCI139434

  20. Song, X., X. Wang, Z. Liu, and Z. Yu. 2020. Role of GPX4-mediated ferroptosis in the sensitivity of triple negative breast cancer cells to gefitinib. Frontiers in Oncology 10: 597434. https://doi.org/10.3389/fonc.2020.597434.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Yang, W.S., R. SriRamaratnam, M.E. Welsch, K. Shimada, R. Skouta, V.S. Viswanathan, J.H. Cheah, P.A. Clemons, A.F. Shamji, C.B. Clish, L.M. Brown, A.W. Girotti, V.W. Cornish, S.L. Schreiber, and B.R. Stockwell. 2014. Regulation of ferroptotic cancer cell death by GPX4. Cell 156 (1–2): 317–331. https://doi.org/10.1016/j.cell.2013.12.010.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Yang, L., S. Tian, Y. Chen, C. Miao, Y. Zhao, R. Wang, and Q. Zhang. 2021. Ferroptosis-related gene model to predict overall survival of ovarian carcinoma. Journal of Oncology 2021: 6687391. https://doi.org/10.1155/2021/6687391.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Wu, J., H. Zhang, L. Li, M. Hu, L. Chen, B. Xu, and Q. Song. 2020. A nomogram for predicting overall survival in patients with low-grade endometrial stromal sarcoma: A population-based analysis. Cancer Communications (Lond) 40 (7): 301–312. https://doi.org/10.1002/cac2.12067.

    Article  Google Scholar 

  24. Hanzelmann, S., R. Castelo, and J. Guinney. 2013. GSVA: Gene set variation analysis for microarray and RNA-seq data. BMC Bioinformatics 14: 7. https://doi.org/10.1186/1471-2105-14-7.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Ma, X., E. Bi, Y. Lu, P. Su, C. Huang, L. Liu, Q. Wang, M. Yang, M.F. Kalady, J. Qian, A. Zhang, A.A. Gupte, D.J. Hamilton, C. Zheng, and Q. Yi. 2019. Cholesterol induces CD8(+) T cell exhaustion in the tumor microenvironment. Cell Metabolism 30 (1): 143–156. https://doi.org/10.1016/j.cmet.2019.04.002.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Wang, Z., J. Zhang, S. Luo, and X. Zhao. 2021. Prognostic significance of systemic immune-inflammation index in patients with diffuse large B-cell lymphoma. Frontiers in Oncology 11: 655259. https://doi.org/10.3389/fonc.2021.655259.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Shang, Y., M. Luo, F. Yao, S. Wang, Z. Yuan, and Y. Yang. 2020. Ceruloplasmin suppresses ferroptosis by regulating iron homeostasis in hepatocellular carcinoma cells. Cellular Signalling 72: 109633. https://doi.org/10.1016/j.cellsig.2020.109633.

    Article  CAS  PubMed  Google Scholar 

  28. Huang, H., Y. Qiu, G. Huang, X. Zhou, X. Zhou, and W. Luo. 2019. Value of ferritin heavy chain (FTH1) expression in diagnosis and prognosis of renal cell carcinoma. Medical Science Monitor 25: 3700–3715. https://doi.org/10.12659/MSM.914162

  29. Taguchi, T., M. Kurata, I. Onishi, Y. Kinowaki, Y. Sato, S. Shiono, S. Ishibashi, M. Ikeda, M. Yamamoto, M. Kitagawa, and K. Yamamoto. 2021. SECISBP2 is a novel prognostic predictor that regulates selenoproteins in diffuse large B-cell lymphoma. Laboratory Investigation 101 (2): 218–227. https://doi.org/10.1038/s41374-020-00495-0.

    Article  CAS  PubMed  Google Scholar 

  30. Sun, X., Z. Ou, M. Xie, R. Kang, Y. Fan, X. Niu, H. Wang, L. Cao, and D. Tang. 2015. HSPB1 as a novel regulator of ferroptotic cancer cell death. Oncogene 34 (45): 5617–5625. https://doi.org/10.1038/onc.2015.32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Li, L., W. Wang, R. Zhang, J. Liu, J. Yu, X. Wu, Y. Xu, M. Ma, and J. Huang. 2017. High expression of LAMP2 predicts poor prognosis in patients with esophageal squamous cell carcinoma. Cancer Biomarkers 19 (3): 305–311. https://doi.org/10.3233/CBM-160469.

    Article  CAS  PubMed  Google Scholar 

  32. Thakur, V.S., B. Aguila, A. Brett-Morris, C.J. Creighton, and S.M. Welford. 2019. Spermidine/spermine N1-acetyltransferase 1 is a gene-specific transcriptional regulator that drives brain tumor aggressiveness. Oncogene 38 (41): 6794–6800. https://doi.org/10.1038/s41388-019-0917-0.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Visweshwaran, S.P., P.A. Thomason, R. Guerois, S. Vacher, E.V. Denisov, L.A. Tashireva, M.E. Lomakina, C. Lazennec-Schurdevin, G. Lakisic, S. Lilla, N. Molinie, V. Henriot, Y. Mechulam, A.Y. Alexandrova, N.V. Cherdyntseva, I. Bieche, E. Schmitt, R.H. Insall, and A. Gautreau. 2018. The trimeric coiled-coil HSBP1 protein promotes WASH complex assembly at centrosomes. The EMBO Jounal 37(13). https://doi.org/10.15252/embj.201797706

  34. Xu, Y.F., Y. Yi, S.J. Qiu, Q. Gao, Y.W. Li, C.X. Dai, M.Y. Cai, M.J. Ju, J. Zhou, B.H. Zhang, and J. Fan. 2010. PEBP1 downregulation is associated to poor prognosis in HCC related to hepatitis B infection. Journal of Hepatology 53 (5): 872–879. https://doi.org/10.1016/j.jhep.2010.05.019.

    Article  CAS  PubMed  Google Scholar 

  35. Lin, H., X. Chen, C. Zhang, T. Yang, Z. Deng, Y. Song, L. Huang, F. Li, Q. Li, S. Lin, and D. Jin. 2021. EF24 induces ferroptosis in osteosarcoma cells through HMOX1. Biomedicine & Pharmacotherapy 136: 111202. https://doi.org/10.1016/j.biopha.2020.111202.

    Article  CAS  Google Scholar 

  36. Chen, P., L. Wang, S. Sun, Q. Zhou, Z. Zeng, M. Hu, M. Hussain, C. Lu, and H. Du. 2020. High-throughput screening suggests glutathione synthetase as an anti-tumor target of polydatin using human proteome chip. International Journal of Biological Macromolecules 161: 1230–1239. https://doi.org/10.1016/j.ijbiomac.2020.06.061.

    Article  CAS  PubMed  Google Scholar 

  37. Huang, S.F., A. Othman, A. Koshkin, S. Fischer, D. Fischer, N. Zamboni, K. Ono, T. Sawa, and O.O. Ogunshola. 2020. Astrocyte glutathione maintains endothelial barrier stability. Redox Biology 34: 101576. https://doi.org/10.1016/j.redox.2020.101576.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Signolet, I., R. Chenouard, F. Oca, M. Barth, P. Reynier, M.C. Denis, and G. Simard. 2016. Recurrent isolated neonatal hemolytic anemia: think about glutathione synthetase deficiency. Pediatrics 138(3). https://doi.org/10.1542/peds.2015-4324

  39. Tamma, R., G. Ranieri, G. Ingravallo, T. Annese, A. Oranger, F. Gaudio, P. Musto, G. Specchia, and D. Ribatti. 2020. Inflammatory cells in diffuse large B cell lymphoma. Journal of Clinical Medicine 9(8). https://doi.org/10.3390/jcm9082418

  40. Xu, H., D. Ye, M. Ren, H. Zhang, and F. Bi. 2021. Ferroptosis in the tumor microenvironment: Perspectives for immunotherapy. Trends in Molecular Medicine. https://doi.org/10.1016/j.molmed.2021.06.014.

    Article  PubMed  Google Scholar 

  41. Xu, C., S. Sun, T. Johnson, R. Qi, S. Zhang, J. Zhang, and K. Yang. 2021. The glutathione peroxidase Gpx4 prevents lipid peroxidation and ferroptosis to sustain Treg cell activation and suppression of antitumor immunity. Cell Reports 35 (11): 109235. https://doi.org/10.1016/j.celrep.2021.109235.

    Article  CAS  PubMed  Google Scholar 

  42. DiLillo, D.J., K. Yanaba, and T.F. Tedder. 2010. B cells are required for optimal CD4+ and CD8+ T cell tumor immunity: Therapeutic B cell depletion enhances B16 melanoma growth in mice. The Journal of Immunology 184 (7): 4006–4016. https://doi.org/10.4049/jimmunol.0903009.

    Article  CAS  PubMed  Google Scholar 

  43. Yao, Y., Z. Chen, H. Zhang, C. Chen, M. Zeng, J. Yunis, Y. Wei, Y. Wan, N. Wang, M. Zhou, C. Qiu, Q. Zeng, H.S. Ong, H. Wang, F.V. Makota, Y. Yang, Z. Yang, N. Wang, J. Deng, C. Shen, Y. Xia, L. Yuan, Z. Lian, Y. Deng, C. Guo, A. Huang, P. Zhou, H. Shi, W. Zhang, H. Yi, D. Li, M. Xia, J. Fu, N. Wu, J.B. de Haan, N. Shen, W. Zhang, Z. Liu, and D. Yu. 2021. Selenium-GPX4 axis protects follicular helper T cells from ferroptosis. Nature Immunology 22 (9): 1127–1139. https://doi.org/10.1038/s41590-021-00996-0.

    Article  CAS  PubMed  Google Scholar 

  44. Li, Q., S. Teitz-Tennenbaum, E.J. Donald, M. Li, and A.E. Chang. 2009. In vivo sensitized and in vitro activated B cells mediate tumor regression in cancer adoptive immunotherapy. The Journal of Immunology 183 (5): 3195–3203. https://doi.org/10.4049/jimmunol.0803773.

    Article  CAS  PubMed  Google Scholar 

  45. Hu, Z., Y. Mi, H. Qian, N. Guo, A. Yan, Y. Zhang, and X. Gao. 2020. A potential mechanism of temozolomide resistance in glioma-ferroptosis. Frontiers in Oncology 10: 897. https://doi.org/10.3389/fonc.2020.00897.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Lewis, T., D.B. Corcoran, D.E. Thurston, P.J. Giles, K. Ashelford, E.J. Walsby, C.D. Fegan, A. Pepper, R.K. Miraz, and C. Pepper. 2021. Novel pyrrolobenzodiazepine benzofused hybrid molecules inhibit NF-kappaB activity and synergise with bortezomib and ibrutinib in hematological cancers. Haematologica 106 (4): 958–967. https://doi.org/10.3324/haematol.2019.238584.

    Article  CAS  PubMed  Google Scholar 

  47. Schmitt, A., W. Xu, P. Bucher, M. Grimm, M. Konantz, H. Horn, M. Zapukhlyak, P. Berning, M. Brandle, M.A. Jarboui, C. Schonfeld, K. Boldt, A. Rosenwald, G. Ott, M. Grau, P. Klener, P. Vockova, C. Lengerke, G. Lenz, K. Schulze-Osthoff, and S. Hailfinger. 2021. Dimethyl fumarate induces ferroptosis and impairs NF-kappaB/STAT3 signaling in DLBCL. Blood 138 (10): 871–884. https://doi.org/10.1182/blood.2020009404.

    Article  CAS  PubMed  Google Scholar 

  48. Mancini, F., C. Landolfi, M. Muzio, L. Aquilini, L. Soldo, I. Coletta, A. Guglielmotti, A. Mantovani, M. Pinza, and C. Milanese. 2003. Acetaminophen down-regulates interleukin-1beta-induced nuclear factor-kappaB nuclear translocation in a human astrocytic cell line. Neuroscience Letters 353 (2): 79–82. https://doi.org/10.1016/j.neulet.2003.08.074.

    Article  CAS  PubMed  Google Scholar 

  49. Altinoz, M.A., and R. Korkmaz. 2004. NF-kappaB, macrophage migration inhibitory factor and cyclooxygenase-inhibitions as likely mechanisms behind the acetaminophen- and NSAID-prevention of the ovarian cancer. Neoplasma 51 (4): 239–247.

    CAS  PubMed  Google Scholar 

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Funding

This study was supported by a grant from the National Scientific Foundation of China to XPY (32070890), the Key Special Project of Ministry of Science and Technology, China (2019YFC1316200), and a grant from the National Scientific Foundation of China to XPY (81671539).

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Author notes

  1. Xiang-Ping Yang and Liu Huang are contributed equally.

Authors and Affiliations

  1. Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan, 430030, China

    Junmei Weng, Huicheng Liu & Xiang-Ping Yang

  2. Department of Oncology, Tongji Hospital, Tongji Medical College, HUST, Wuhan, 430030, China

    Lian Chen & Liu Huang

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  1. Junmei Weng
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  2. Lian Chen
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Contributions

Junmei Weng performed the bioinformatics analysis, prepared these figures, and drafted the manuscript. Lian Chen and Huicheng Liu participated in discussion. Xiang-Ping Yang and Liu Huang designed this study and revised the manuscript. All the authors read and approved the final manuscript.

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Correspondence to Xiang-Ping Yang or Liu Huang.

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Weng, J., Chen, L., Liu, H. et al. Ferroptosis Markers Predict the Survival, Immune Infiltration, and Ibrutinib Resistance of Diffuse Large B cell Lymphoma. Inflammation 45, 1146–1161 (2022). https://doi.org/10.1007/s10753-021-01609-6

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