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Combinatorial Chemistry & High Throughput Screening

Editor-in-Chief

ISSN (Print): 1386-2073
ISSN (Online): 1875-5402

Research Article

Comprehensive Analysis of Cuproptosis Genes and Identification of Cuproptosis Subtypes in Breast Cancer

Author(s): Jialin Li, Lei Li*, Yi Dong, Bin Zhong and Wei Yin

Volume 26, Issue 8, 2023

Published on: 31 January, 2023

Page: [1578 - 1593] Pages: 16

DOI: 10.2174/1386207326666230120112904

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Open Access Journals Promotions 2
Abstract

Background: Copper-induced death (cuproptosis) is copper-dependent regulated cell death, which is different from known death mechanisms and is dependent on mitochondrial respiration. However, its effect on breast cancer (BRCA) is unclear.

Objective: The objective of this study is to explore the important clinical significance of cuproptosis genes and to provide a new idea for guiding the personalized immunotherapy strategy of BRCA patients.

Materials and Methods: We collected cuproptosis genes from published work. The gene alteration, differential expression, and prognostic value of cuproptosis genes were explored in BRCA based on TCGA database. We identified two subtypes (clusters A and B) by performing unsupervised clustering. The difference between two clusters was deeply explored, including clinical features, differential expressed genes (DEGs), pathways, and immune cell infiltration. Based on the DEGs between two clusters, a cuproptosis score was constructed and its predictive capability for overall survival of BRCA patients was validated.

Results and Discussion: Patients with high cuproptosis score have worse survival status, with an increased infiltration level of most immune cells. Further analysis suggested that BRCA patients with high cuproptosis score may be sensitive to immune checkpoint inhibitor (ICI) treatment.

Conclusion: Our findings may improve our understanding of cuproptosis in BRCA and may distinguish patients suitable for ICI treatment.

Keywords: Cuproptosis, BRCA, subtypes, ICI treatment, cell death, copper-induced death.

Graphical Abstract
[1]
Kahlson, M.A.; Dixon, S.J. Copper-induced cell death. Science, 2022, 375(6586), 1231-1232.
[http://dx.doi.org/10.1126/science.abo3959] [PMID: 35298241]
[2]
Tsvetkov, P.; Coy, S.; Petrova, B.; Dreishpoon, M.; Verma, A.; Abdusamad, M.; Rossen, J.; Joesch-Cohen, L.; Humeidi, R.; Spangler, R.D.; Eaton, J.K.; Frenkel, E.; Kocak, M.; Corsello, S.M.; Lutsenko, S.; Kanarek, N.; Santagata, S.; Golub, T.R. Copper induces cell death by targeting lipoylated TCA cycle proteins. Science, 2022, 375(6586), 1254-1261.
[http://dx.doi.org/10.1126/science.abf0529] [PMID: 35298263]
[3]
Yang, Z.; Ming, X.; Huang, S.; Yang, M.; Zhou, X.; Fang, J. Comprehensive analysis of m6A regulators characterized by the immune cell infiltration in head and neck squamous cell carcinoma to aid immunotherapy and chemotherapy. Front. Oncol., 2021, 11, 764798.
[http://dx.doi.org/10.3389/fonc.2021.764798] [PMID: 34917507]
[4]
Bagchi, S.; Yuan, R.; Engleman, E.G. Immune checkpoint inhibitors for the treatment of cancer: Clinical impact and mechanisms of response and resistance. Annu. Rev. Pathol., 2021, 16(1), 223-249.
[http://dx.doi.org/10.1146/annurev-pathol-042020-042741] [PMID: 33197221]
[5]
Pinato, D.J.; Howlett, S.; Ottaviani, D.; Urus, H.; Patel, A.; Mineo, T.; Brock, C.; Power, D.; Hatcher, O.; Falconer, A.; Ingle, M.; Brown, A.; Gujral, D.; Partridge, S.; Sarwar, N.; Gonzalez, M.; Bendle, M.; Lewanski, C.; Newsom-Davis, T.; Allara, E.; Bower, M. Association of prior antibiotic treatment with survival and response to immune checkpoint inhibitor therapy in patients with cancer. JAMA Oncol., 2019, 5(12), 1774-1778.
[http://dx.doi.org/10.1001/jamaoncol.2019.2785] [PMID: 31513236]
[6]
Liu, D.; Lin, J.R.; Robitschek, E.J.; Kasumova, G.G.; Heyde, A.; Shi, A.; Kraya, A.; Zhang, G.; Moll, T.; Frederick, D.T.; Chen, Y.A.; Wang, S.; Schapiro, D.; Ho, L.L.; Bi, K.; Sahu, A.; Mei, S.; Miao, B.; Sharova, T.; Alvarez-Breckenridge, C.; Stocking, J.H.; Kim, T.; Fadden, R.; Lawrence, D.; Hoang, M.P.; Cahill, D.P.; Malehmir, M.; Nowak, M.A.; Brastianos, P.K.; Lian, C.G.; Ruppin, E.; Izar, B.; Herlyn, M.; Van Allen, E.M.; Nathanson, K.; Flaherty, K.T.; Sullivan, R.J.; Kellis, M.; Sorger, P.K.; Boland, G.M. Evolution of delayed resistance to immunotherapy in a melanoma responder. Nat. Med., 2021, 27(6), 985-992.
[http://dx.doi.org/10.1038/s41591-021-01331-8] [PMID: 33941922]
[7]
Zhang, X.; Zhang, X.; Li, G.; Hao, Y.; Liu, L.; Zhang, L.; Chen, Y.; Wu, J.; Wang, X.; Yang, S.; Xu, S. A novel necroptosis-associated lncRNA signature can impact the immune status and predict the outcome of breast cancer. J. Immunol. Res., 2022, 2022, 1-21.
[http://dx.doi.org/10.1155/2022/3143511] [PMID: 35578667]
[8]
Cuenca-Micó, O.; Delgado-González, E.; Anguiano, B.; Vaca-Paniagua, F.; Medina-Rivera, A.; Rodríguez-Dorantes, M.; Aceves, C. Effects of molecular iodine/chemotherapy in the immune component of breast cancer tumoral microenvironment. Biomolecules, 2021, 11(10), 1501.
[http://dx.doi.org/10.3390/biom11101501] [PMID: 34680134]
[9]
Vishnubalaji, R.; Alajez, N.M. Epigenetic regulation of triple negative breast cancer (TNBC) by TGF-β signaling. Sci. Rep., 2021, 11(1), 15410.
[http://dx.doi.org/10.1038/s41598-021-94514-9] [PMID: 34326372]
[10]
Wang, J.; Xiang, H.; Lu, Y.; Wu, T. Role and clinical significance of TGF β1 and TGF βR1 in malignant tumors (Review). Int. J. Mol. Med., 2021, 47(4), 55.
[http://dx.doi.org/10.3892/ijmm.2021.4888] [PMID: 33604683]
[11]
Chang, L.S.; Barroso-Sousa, R.; Tolaney, S.M.; Hodi, F.S.; Kaiser, U.B.; Min, L. Endocrine toxicity of cancer immunotherapy targeting immune checkpoints. Endocr. Rev., 2019, 40(1), 17-65.
[http://dx.doi.org/10.1210/er.2018-00006] [PMID: 30184160]
[12]
Minami, H.; Kiyota, N.; Kimbara, S.; Ando, Y.; Shimokata, T.; Ohtsu, A.; Fuse, N.; Kuboki, Y.; Shimizu, T.; Yamamoto, N.; Nishio, K.; Kawakami, Y.; Nihira, S.; Sase, K.; Nonaka, T.; Takahashi, H.; Komori, Y.; Kiyohara, K. Guidelines for clinical evaluation of anti‐cancer drugs. Cancer Sci., 2021, 112(7), 2563-2577.
[http://dx.doi.org/10.1111/cas.14967] [PMID: 33990993]
[13]
Harris, E.D. Copper as a cofactor and regulator of copper,zinc superoxide dismutase. J. Nutr., 1992, 122(3)(Suppl. 3), 636-640.
[http://dx.doi.org/10.1093/jn/122.suppl_3.636] [PMID: 1542024]
[14]
Solano, F. On the metal cofactor in the tyrosinase family. Int. J. Mol. Sci., 2018, 19(2), 633.
[http://dx.doi.org/10.3390/ijms19020633] [PMID: 29473882]
[15]
Jiang, Y.; Huo, Z.; Qi, X.; Zuo, T.; Wu, Z. Copper-induced tumor cell death mechanisms and antitumor theragnostic applications of copper complexes. Nanomedicine (Lond.), 2022, 17(5), 303-324.
[http://dx.doi.org/10.2217/nnm-2021-0374] [PMID: 35060391]
[16]
Mufti, A.R.; Burstein, E.; Duckett, C.S. XIAP: Cell death regulation meets copper homeostasis. Arch. Biochem. Biophys., 2007, 463(2), 168-174.
[http://dx.doi.org/10.1016/j.abb.2007.01.033] [PMID: 17382285]
[17]
Han, J.; Hu, Y.; Liu, S.; Jiang, J.; Wang, H. A newly established cuproptosis-associated long non-coding RNA signature for predicting prognosis and indicating immune microenvironment features in soft tissue sarcoma. J. Oncol., 2022, 2022, 1-27.
[http://dx.doi.org/10.1155/2022/8489387] [PMID: 35847354]
[18]
De Luca, A.; Barile, A.; Arciello, M.; Rossi, L. Copper homeostasis as target of both consolidated and innovative strategies of anti-tumor therapy. J. Trace Elem. Med. Biol., 2019, 55, 204-213.
[http://dx.doi.org/10.1016/j.jtemb.2019.06.008] [PMID: 31345360]
[19]
Shanbhag, V.C.; Gudekar, N.; Jasmer, K.; Papageorgiou, C.; Singh, K.; Petris, M.J. Copper metabolism as a unique vulnerability in cancer. Biochim. Biophys. Acta Mol. Cell Res., 2021, 1868(2), 118893.
[http://dx.doi.org/10.1016/j.bbamcr.2020.118893] [PMID: 33091507]
[20]
Li, Y. Copper homeostasis: Emerging target for cancer treatment. IUBMB Life, 2020, 72(9), 1900-1908.
[http://dx.doi.org/10.1002/iub.2341] [PMID: 32599675]
[21]
Liu, L.; Bai, X.; Wang, J.; Tang, X.R.; Wu, D.H.; Du, S.S.; Du, X.J.; Zhang, Y.W.; Zhu, H.B.; Fang, Y.; Guo, Z.Q.; Zeng, Q.; Guo, X.J.; Liu, Z.; Dong, Z.Y. Combination of TMB and CNA stratifies prognostic and predictive responses to immunotherapy across metastatic cancer. Clin. Cancer Res., 2019, 25(24), 7413-7423.
[http://dx.doi.org/10.1158/1078-0432.CCR-19-0558] [PMID: 31515453]
[22]
Singh, N.K.; Kumbhar, A.A.; Pokharel, Y.R.; Yadav, P.N. Anticancer potency of copper(II) complexes of thiosemicarbazones. J. Inorg. Biochem., 2020, 210, 111134.
[http://dx.doi.org/10.1016/j.jinorgbio.2020.111134] [PMID: 32673842]
[23]
Fei, B.L.; Hui, C.N.; Wei, Z.; Kong, L.Y.; Long, J.Y.; Qiao, C.; Chen, Z.F. Copper(II) and iron(III) complexes of chiral dehydroabietic acid derived from natural rosin: Metal effect on structure and cytotoxicity. Metallomics, 2021, 13(4), mfab014.
[http://dx.doi.org/10.1093/mtomcs/mfab014] [PMID: 33765148]
[24]
Lin, L.S.; Huang, T.; Song, J.; Ou, X.Y.; Wang, Z.; Deng, H.; Tian, R.; Liu, Y.; Wang, J.F.; Liu, Y.; Yu, G.; Zhou, Z.; Wang, S.; Niu, G.; Yang, H.H.; Chen, X. Synthesis of copper peroxide nanodots for H2O2 self-supplying chemodynamic therapy. J. Am. Chem. Soc., 2019, 141(25), 9937-9945.
[http://dx.doi.org/10.1021/jacs.9b03457] [PMID: 31199131]
[25]
Song, S.; Zhang, M.; Xie, P.; Wang, S.; Wang, Y. Comprehensive analysis of cuproptosis-related genes and tumor microenvironment infiltration characterization in breast cancer. Front. Immunol., 2022, 13, 978909.
[http://dx.doi.org/10.3389/fimmu.2022.978909] [PMID: 36341328]

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