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Hub gene of disulfidptosis-related immune checkpoints in breast cancer

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Abstract

Disulfidptosis and immune checkpoint genes play an important role in tumor treatment. But there has been less research on the relationship between disulfidptosis and immune checkpoint of breast cancer. The objective of this study was to identify the hub genes of disulfidptosis- related immune checkpoints in breast cancer. We downloaded breast cancer expression data from The Cancer Genome Atlas database. The expression matrix of disulfidptosis-related immune checkpoints genes was established by mathematical method. A protein–protein interaction networks was established based on this expression matrix, and differential expression analysis was performed between normal and tumor samples. Additionally, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to functionally annotate putative diferentially expressed genes. Two hub genes CD80 and CD276 were obtained by mathematical statistics and machine learning. Differential expression of these two genes, prognostic survival analysis, combined diagnostic ROC curve and immune results all showed that they were closely related to the occurrence, development and death of breast tumors. The results of this study open up a new way to explore immunotherapy for breast cancer.

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The datasets used and/or analysed during the current study available from the corresponding author on reasonable request.

References

  1. Li X, Li S, Li B, Li Y, Aman S, Xia K, Yang Y, Ahmad B, Wu H. Acetylation of ELF5 suppresses breast cancer progression by promoting its degradation and targeting CCND1. NPJ Precis Oncol. 2021;5(1):20. https://doi.org/10.1038/s41698-021-00158-3. (PMID: 33742100; PMCID: PMC7979705).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Tian X, Yu H, Li D, Jin G, Dai S, Gong P, Kong C, Wang X. The miR-5694/AF9/Snail Axis Provides Metastatic Advantages and a Therapeutic Target in Basal-like Breast Cancer. Mol Ther. 2021;29(3):1239–57. https://doi.org/10.1016/j.ymthe.2020.11.022. (Epub 2020 Nov 20. PMID: 33221433; PMCID: PMC7934584).

    Article  CAS  PubMed  Google Scholar 

  3. Romero-Moreno R, Curtis KJ, Coughlin TR, Miranda-Vergara MC, Dutta S, Natarajan A, Facchine BA, Jackson KM, Nystrom L, Li J, Kaliney W, Niebur GL, Littlepage LE. The CXCL5/CXCR2 axis is sufficient to promote breast cancer colonization during bone metastasis. Nat Commun. 2019;10(1):4404. https://doi.org/10.1038/s41467-019-12108-6. (PMID: 31562303; PMCID: PMC6765048).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Sears CR, Peikert T, Possick JD, Naidoo J, Nishino M, Patel SP, Camus P, Gaga M, Garon EB, Gould MK, Limper AH, Montgrain PR, Travis WD, Rivera MP. Knowledge gaps and research priorities in immune checkpoint inhibitor-related pneumonitis. An official American thoracic society research statement. Am J Respir Crit Care Med. 2019;200(6):e31–43. https://doi.org/10.1164/rccm.201906-1202ST.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Wang G, Dong Y, Yang Y, Zhang W, Liu N, Wei Y. PD-L1 rs2890658 Polymorphism Increases Risk for Non-Small-Cell Lung Cancer in Northern China Population Based on Experimental Data and Meta-Analysis. Contrast Media Mol Imaging. 2022;2022:8433489. https://doi.org/10.1155/2022/8433489. (PMID: 35992543; PMCID: PMC9363189).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Satoh Y, Kotani H, Iida Y, Taniura T, Notsu Y, Harada M. Supplementation of l-arginine boosts the therapeutic efficacy of anticancer chemoimmunotherapy. Cancer Sci. 2020;111(7):2248–58. https://doi.org/10.1111/cas.14490. (Epub 2020 Jun 12. PMID: 32426941; PMCID: PMC7484823).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Thomas M, Armenti ST, Ayres MB, Demirci H. Uveal effusion after immune checkpoint inhibitor therapy. JAMA Ophthalmol. 2018;136(5):553–6. https://doi.org/10.1001/jamaophthalmol.2018.0920. (PMID: 29677240; PMCID: PMC6145660).

    Article  PubMed  PubMed Central  Google Scholar 

  8. Doroshow DB, Bhalla S, Beasley MB, Sholl LM, Kerr KM, Gnjatic S, Wistuba II, Rimm DL, Tsao MS, Hirsch FR. PD-L1 as a biomarker of response to immune-checkpoint inhibitors. Nat Rev Clin Oncol. 2021;18(6):345–62. https://doi.org/10.1038/s41571-021-00473-5. (Epub 2021 Feb 12 PMID: 33580222).

    Article  CAS  PubMed  Google Scholar 

  9. Shin CS, Mishra P, Watrous JD, Carelli V, D’Aurelio M, Jain M, Chan DC. The glutamate/cystine xCT antiporter antagonizes glutamine metabolism and reduces nutrient flexibility. Nat Commun. 2017;8:15074. https://doi.org/10.1038/ncomms15074. (PMID: 28429737; PMCID: PMC5413954).

    Article  PubMed  PubMed Central  Google Scholar 

  10. Liu X, Nie L, Zhang Y, Yan Y, Wang C, Colic M, Olszewski K, Horbath A, Chen X, Lei G, Mao C, Wu S, Zhuang L, Poyurovsky MV, James You M, Hart T, Billadeau DD, Chen J, Gan B. Actin cytoskeleton vulnerability to disulfide stress mediates disulfidptosis. Nat Cell Biol. 2023;25(3):404–14. https://doi.org/10.1038/s41556-023-01091-2. (Epub 2023 Feb 6. PMID: 36747082; PMCID: PMC10027392).

    Article  CAS  PubMed  Google Scholar 

  11. Hu FF, Liu CJ, Liu LL, Zhang Q, Guo AY. Expression profile of immune checkpoint genes and their roles in predicting immunotherapy response. Brief Bioinform. 2021;22(3):bbaa176. https://doi.org/10.1093/bib/bbaa176. (PMID: 32814346).

    Article  CAS  PubMed  Google Scholar 

  12. Newman AM, Liu CL, Green MR, Gentles AJ, Feng W, Xu Y, Hoang CD, Diehn M, Alizadeh AA. Robust enumeration of cell subsets from tissue expression profiles. Nat Methods. 2015;12(5):453–7. https://doi.org/10.1038/nmeth.3337. (Epub 2015 Mar 30. PMID: 25822800; PMCID: PMC4739640).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Cong F, Yu H, Gao X. Expression of CD24 and B7–H3 in breast cancer and the clinical significance. Oncol Lett. 2017;14(6):7185–90. https://doi.org/10.3892/ol.2017.7142. (Epub 2017 Oct 5. PMID: 29344150; PMCID: PMC5754897).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Liang Y, Tang H, Guo J, Qiu X, Yang Z, Ren Z, Sun Z, Bian Y, Xu L, Xu H, Shen J, Han Y, Dong H, Peng H, Fu YX. Targeting IFNα to tumor by anti-PD-L1 creates feedforward antitumor responses to overcome checkpoint blockade resistance. Nat Commun. 2018;9(1):4586. https://doi.org/10.1038/s41467-018-06890-y. (PMID: 30389912; PMCID: PMC6214895).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Wang J, Li Z. TREM2 is a prognostic biomarker and correlated with an immunosuppressive microenvironment in thyroid cancer. Dis Markers. 2022;2022:1807386. https://doi.org/10.1155/2022/1807386. (PMID: 36438899; PMCID: PMC9683966).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Chen Y, Wang Y, Luo H, Meng X, Zhu W, Wang D, Zeng H, Zhang H. The frequency and inter-relationship of PD-L1 expression and tumour mutational burden across multiple types of advanced solid tumours in China. Exp Hematol Oncol. 2020;9:17. https://doi.org/10.1186/s40164-020-00173-3. (PMID: 32775040; PMCID: PMC7397649).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Hodi FS, O’Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, Gonzalez R, Robert C, Schadendorf D, Hassel JC, Akerley W, van den Eertwegh AJ, Lutzky J, Lorigan P, Vaubel JM, Linette GP, Hogg D, Ottensmeier CH, Lebbé C, Peschel C, Quirt I, Clark JI, Wolchok JD, Weber JS, Tian J, Yellin MJ, Nichol GM, Hoos A, Urba WJ. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010;363(8):711–23. https://doi.org/10.1056/NEJMoa1003466. (Epub 2010 Jun 5. Erratum in: N Engl J Med. 2010 Sep 23;363(13):1290. PMID: 20525992; PMCID: PMC3549297).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Skertich NJ, Chu F, Tarhoni IAM, Szajek S, Borgia JA, Madonna MB. Expression of immunomodulatory checkpoint molecules in drug-resistant neuroblastoma: an exploratory study. Cancers (Basel). 2022;14(3):751. https://doi.org/10.3390/cancers14030751. (PMID: 35159017; PMCID: PMC8833944).

    Article  CAS  PubMed  Google Scholar 

  19. Sun F, Yu X, Ju R, Wang Z, Wang Y. Antitumor responses in gastric cancer by targeting B7H3 via chimeric antigen receptor T cells. Cancer Cell Int. 2022;22(1):50. https://doi.org/10.1186/s12935-022-02471-8. (PMID: 35101032; PMCID: PMC8802437).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Avci O, Çavdar E, İriağaç Y, Karaboyun K, Çelikkol A, Özçağlayan TİK, Öznur M, Gürdal SÖ, Şeber ES. Soluble B7H3 level in breast cancer and its relationship with clinicopathological variables and T cell infiltration. Contemp Oncol (Pozn). 2022;26(1):27–31. https://doi.org/10.5114/wo.2022.113502. (Epub 2022 Feb 11. PMID: 35506036; PMCID: PMC9052342).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Si Y, Chen K, Kim S, Zhou Z, Zhou L, Liu XM. Abstract 5958: CD276/CD47-targeted antibody-drug conjugates to treat triple-negative breast cancers. Cancer Res. 2022;82(12_Supplement):5958. https://doi.org/10.1158/1538-7445.AM2022-5958.

    Article  Google Scholar 

  22. Blenman KRM, He TF, Frankel PH, Ruel NH, Schwartz EJ, Krag DN, Tan LK, Yim JH, Mortimer JE, Yuan Y, Lee PP. Sentinel lymph node B cells can predict disease-free survival in breast cancer patients. NPJ Breast Cancer. 2018;4:28. https://doi.org/10.1038/s41523-018-0081-7. (PMID: 30155518; PMCID: PMC6107630).

    Article  PubMed  PubMed Central  Google Scholar 

  23. Hu Q, Hong Y, Qi P, Lu G, Mai X, Xu S, He X, Guo Y, Gao L, Jing Z, Wang J, Cai T, Zhang Y. Atlas of breast cancer infiltrated B-lymphocytes revealed by paired single-cell RNA-sequencing and antigen receptor profiling. Nat Commun. 2021;12(1):2186. https://doi.org/10.1038/s41467-021-22300-2. (PMID: 33846305; PMCID: PMC8042001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Chapoval AI, Ni J, Lau JS, Wilcox RA, Flies DB, Liu D, Dong H, Sica GL, Zhu G, Tamada K, Chen L. B7–H3: a costimulatory molecule for T cell activation and IFN-gamma production. Nat Immunol. 2001;2(3):269–74. https://doi.org/10.1038/85339. (PMID: 11224528).

    Article  CAS  PubMed  Google Scholar 

  25. Suh WK, Gajewska BU, Okada H, Gronski MA, Bertram EM, Dawicki W, Duncan GS, Bukczynski J, Plyte S, Elia A, Wakeham A, Itie A, Chung S, Da Costa J, Arya S, Horan T, Campbell P, Gaida K, Ohashi PS, Watts TH, Yoshinaga SK, Bray MR, Jordana M, Mak TW. The B7 family member B7–H3 preferentially down-regulates T helper type 1-mediated immune responses. Nat Immunol. 2003;4(9):899–906. https://doi.org/10.1038/ni967. (Epub 2003 Aug 17 PMID: 12925852).

    Article  CAS  PubMed  Google Scholar 

  26. Lee YH, Martin-Orozco N, Zheng P, Li J, Zhang P, Tan H, Park HJ, Jeong M, Chang SH, Kim BS, Xiong W, Zang W, Guo L, Liu Y, Dong ZJ, Overwijk WW, Hwu P, Yi Q, Kwak L, Yang Z, Mak TW, Li W, Radvanyi LG, Ni L, Liu D, Dong C. Inhibition of the B7–H3 immune checkpoint limits tumor growth by enhancing cytotoxic lymphocyte function. Cell Res. 2017;27(8):1034–45. https://doi.org/10.1038/cr.2017.90. (Epub 2017 Jul 7. PMID: 28685773; PMCID: PMC5539354).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Yang S, Wei W, Zhao Q. B7–H3, a checkpoint molecule, as a target for cancer immunotherapy. Int J Biol Sci. 2020;16(11):1767–73. https://doi.org/10.7150/ijbs.41105. (PMID: 32398947; PMCID: PMC7211166).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Li Y, Yang X, Wu Y, Zhao K, Ye Z, Zhu J, Xu X, Zhao X, Xing C. B7–H3 promotes gastric cancer cell migration and invasion. Oncotarget. 2017;8(42):71725–35. https://doi.org/10.18632/oncotarget.17847. (PMID: 29069741; PMCID: PMC5641084).

    Article  PubMed  PubMed Central  Google Scholar 

  29. Jin Y, Zhang P, Li J, Zhao J, Liu C, Yang F, et al. B7–H3 in combination with regulatory T cell is associated with tumor progression in primary human non-small cell lung cancer. Int J Clin Exp Pathol. 2015;8:13987–95.

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Lim S, Liu H, Madeira da Silva L, Arora R, Liu Z, Phillips JB, Schmitt DC, Vu T, McClellan S, Lin Y, Lin W, Piazza GA, Fodstad O, Tan M. Immunoregulatory protein B7–H3 reprograms glucose metabolism in cancer cells by ROS-mediated stabilization of HIF1α. Cancer Res. 2016;76(8):2231–42. https://doi.org/10.1158/0008-5472.CAN-15-1538. (Epub 2016 Apr 5. PMID: 27197253; PMCID: PMC4874665).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Nunes-Xavier CE, Karlsen KF, Tekle C, Pedersen C, Øyjord T, Hongisto V, Nesland JM, Tan M, Sahlberg KK, Fodstad Ø. Decreased expression of B7–H3 reduces the glycolytic capacity and sensitizes breast cancer cells to AKT/mTOR inhibitors. Oncotarget. 2016;7(6):6891–901. https://doi.org/10.18632/oncotarget.6902. (PMID: 26771843; PMCID: PMC4872756).

    Article  PubMed  PubMed Central  Google Scholar 

  32. Wei Y, Wang D, Jin F, Bian Z, Li L, Liang H, Li M, Shi L, Pan C, Zhu D, Chen X, Hu G, Liu Y, Zhang CY, Zen K. Pyruvate kinase type M2 promotes tumour cell exosome release via phosphorylating synaptosome-associated protein 23. Nat Commun. 2017;8:14041. https://doi.org/10.1038/ncomms14041. (PMID: 28067230; PMCID: PMC5228053).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Jain A, Song R, Wakeland EK, Pasare C. T cell-intrinsic IL-1R signaling licenses effector cytokine production by memory CD4 T cells. Nat Commun. 2018;9(1):3185. https://doi.org/10.1038/s41467-018-05489-7. (PMID: 30093707; PMCID: PMC6085393).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. He X, Xu C. Immune checkpoint signaling and cancer immunotherapy. Cell Res. 2020;30(8):660–9. https://doi.org/10.1038/s41422-020-0343-4. (Epub 2020 May 28. PMID: 32467592; PMCID: PMC7395714).

    Article  PubMed  PubMed Central  Google Scholar 

  35. Leng C, Li Y, Qin J, Ma J, Liu X, Cui Y, Sun H, Wang Z, Hua X, Yu Y, Li H, Zhang J, Zheng Y, Wang W, Zhu J, Wang Q. Relationship between expression of PD-L1 and PD-L2 on esophageal squamous cell carcinoma and the antitumor effects of CD8+ T cells. Oncol Rep. 2016;35(2):699–708. https://doi.org/10.3892/or.2015.4435. (Epub 2015 Nov 17 PMID: 26718132).

    Article  CAS  PubMed  Google Scholar 

  36. Saleh RR, Scott JL, Meti N, Perlon D, Fazelzad R, Ocana A, Amir E. Prognostic Value of programmed death ligand-1 expression in solid tumors irrespective of immunotherapy exposure: a systematic review and meta-analysis. Mol Diagn Ther. 2022;26(2):153–68. https://doi.org/10.1007/s40291-022-00576-4. (Epub 2022 Feb 1 PMID: 35106739).

    Article  CAS  PubMed  Google Scholar 

  37. Li Z, Li B, Peng D, Xing H, Wang G, Li P, Wang J, Ye G, Chen J. Expression and clinical significance of PD-1 in hepatocellular carcinoma tissues detected by a novel mouse anti-human PD-1 monoclonal antibody. Int J Oncol. 2018;52(6):2079–92. https://doi.org/10.3892/ijo.2018.4358. (Epub 2018 Apr 4. PMID: 29620156; PMCID: PMC6929674).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Adams S, Loi S, Toppmeyer D, et al. KEYNOTE-086 cohort B: pembrolizumab monotherapy for PD-L1-positive, previously untreated, metastatic triple-negative breast cancer (mTNBC) [abstract]. Cancer Res. 2018;78(4 suppl):PD6-10.

    Google Scholar 

  39. Li Y, Zhang H, Merkher Y, Chen L, Liu N, Leonov S, Chen Y. Recent advances in therapeutic strategies for triple-negative breast cancer. J Hematol Oncol. 2022;15(1):121. https://doi.org/10.1186/s13045-022-01341-0. (PMID: 36038913; PMCID: PMC9422136).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

Acknowledgments to the TCGA databases for providing researchable patient data.

Funding

This study was supported by: (1) Key Laboratory of Tumor Precision Medicine, Hunan colleges and Universities Project (2019-379). (2) Scientific Research Project of Hunan Provincial Health Commission (No. 202202084081).

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Author notes

  1. Ye Wang and Yinmei Deng have contributed equally to this work.

Authors and Affiliations

  1. Department of Thoracic Surgery, Affiliated Hospital (Clinical College) of Xiangnan University, Chenzhou, 423000, Hunan Province, People’s Republic of China

    Ye Wang

  2. Key Laboratory of Medical Imaging and Artifical Intelligence of Hunan Province, Chenzhou, 423000, People’s Republic of China

    Ye Wang, Hui Xie & Sujuan Cao

  3. Department of Nursing, Affiliated Hospital (Clinical College) of Xiangnan University, Chenzhou, 423000, People’s Republic of China

    Yinmei Deng

  4. Department of Radiation Oncology, Affiliated Hospital (Clinical College) of Xiangnan University, Chenzhou, 423000, Hunan Province, People’s Republic of China

    Hui Xie

  5. Department of Oncology, Affiliated Hospital (Clinical College) of Xiangnan University, Chenzhou, 423000, Hunan Province, People’s Republic of China

    Sujuan Cao

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  1. Ye Wang
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Contributions

HX and SC: designed the study, YW and YD: searched, analyzed and interpreted the literature and was a major contributor in writing the manuscript. HX and SC: revised the manuscript.

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Correspondence to Hui Xie or Sujuan Cao.

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Wang, Y., Deng, Y., Xie, H. et al. Hub gene of disulfidptosis-related immune checkpoints in breast cancer. Med Oncol 40, 222 (2023). https://doi.org/10.1007/s12032-023-02073-y

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