Cuproptosis-related gene CEP55 as a biomarker of pancreatic adenocarcinoma via multi-omics techniques and experimental validation
By: Riyuan Zhang, Zixia Xu, Yurui Zhuang, Yuzhe Shi, Ziyi Guo and Chong Chen
References
- Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer Statistics, 2021. CA Cancer J Clin 2021; 71: 7-33. doi: 10.3322/caac.21654
- Moore A, Donahue T. Pancreatic cancer. Jama 2019; 322: 1426. doi: 10.1001/jama.2019.14699
- Rahib L, Smith BD, Aizenberg R, Rosenzweig AB, Fleshman JM, Matrisian LM. Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer Res 2014; 74: 2913-21. doi: 10.1158/0008-5472.Can-14-0155
- Warshaw AL, del Castillo FC. Pancreatic carcinoma. N Engl J Med 1992; 326: 455-65. doi: 10.1056/nejm199202133260706
- Howlader N, Noone AM, Krapcho M, Garshell J, Miller D, Altekruse SF, et al. SEER cancer statistics review, 1975-2009. [internet]. Bethesda, MD, USA: National Cancer Institute; 2012. [cited 2025 Jan 15]. Available at: http://seer.cancer.gov/csr/1975_2012/
- Klepsch V, Hermann-Kleiter N, Do-Dinh P, Jakic B, Offermann A, Efremova M, et al. Nuclear receptor NR2F6 inhibition potentiates responses to PD-L1/PD-1 cancer immune checkpoint blockade. Nat Commun 2018; 9: 1538. doi: 10.1038/s41467-018-04004-2
- Li X, Gulati M, Larson AC, Solheim JC, Jain M, Kumar S, et al. Immune checkpoint blockade in pancreatic cancer: trudging through the immune desert. Semin Cancer Biol 2022; 86: 14-27. doi: 10.1016/j.semcancer.2022.08.009
- Heumann T, Azad N. Next-generation immunotherapy for pancreatic ductal adenocarcinoma: navigating pathways of immune resistance. Cancer Metastasis Rev 2021; 40: 837-62. doi: 10.1007/s10555-021-09981-3
- Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell 2011; 144: 646-74. doi: 10.1016/j.cell.2011.02.013
- Fesik SW. Promoting apoptosis as a strategy for cancer drug discovery. Nat Rev Cancer 2005; 5: 876-85. doi: 10.1038/nrc1736
- Dixon SJ, Lemberg KM, Lamprecht MR, Skouta R, Zaitsev EM, Gleason CE, et al. Ferroptosis: an iron-dependent form of nonapoptotic cell death. Cell 2012; 149: 1060-72. doi: 10.1016/j.cell.2012.03.042
- Stockwell BR, Friedmann Angeli JP, Bayir H, Bush AI, Conrad M, Dixon SJ, et al. Ferroptosis: a regulated cell death nexus linking metabolism, redox biology, and disease. Cell 2017; 171: 273-85. doi: 10.1016/j.cell.2017.09.021
- Shi J, Gao W, Shao F. Pyroptosis: gasdermin-mediated programmed necrotic cell death. Trends Biochem Sci 2017; 42: 245-54. doi: 10.1016/j. tibs.2016.10.004
- Fatokun AA, Dawson VL, Dawson TM. Parthanatos: mitochondrial-linked mechanisms and therapeutic opportunities. Br J Pharmacol 2014; 171: 2000-16. doi: 10.1111/bph.12416
- Tsvetkov P, Coy S, Petrova B, Dreishpoon M, Verma A, Abdusamad M, et al. Copper induces cell death by targeting lipoylated TCA cycle proteins. Science 2022; 375: 1254-61. doi: 10.1126/science.abf0529
- Li SR, Bu LL, Cai L. Cuproptosis: lipoylated TCA cycle proteins-mediated novel cell death pathway. Signal Transduct Target Ther 2022; 7: 158. doi: 10.1038/s41392-022-01014-x
- Sprooten J, De Wijngaert P, Vanmeerbeerk I, Martin S, Vangheluwe P, Schlenner S, et al. Necroptosis in immuno-oncology and cancer immunotherapy. Cells 2020; 9: 1823. doi: 10.3390/cells9081823
- Zhang Z, Zeng X, Wu Y, Liu Y, Zhang X, Song Z. Cuproptosis-related risk score predicts prognosis and characterizes the tumor microenvironment in hepatocellular carcinoma. Front Immunol 2022; 13: 925618. doi: 10.3389/fimmu.2022.925618
- Li Z, Zhang H, Wang X, Wang Q, Xue J, Shi Y, et al. Identification of cuproptosis-related subtypes, characterization of tumor microenvironment infiltration, and development of a prognosis model in breast cancer. Front Immunol 2022; 13: 996836. doi: 10.3389/fimmu.2022.996836
- Ji ZH, Ren WZ, Wang HQ, Gao W, Yuan B. Molecular subtyping based on cuproptosis-related genes and characterization of tumor microenvironment infiltration in kidney renal clear cell carcinoma. Front Oncol 2022; 12: 919083. doi: 10.3389/fonc.2022.919083
- Fang Z, Wang W, Liu Y, Hua J, Liang C, Liu J, et al. Cuproptosis-related gene DLAT as a novel biomarker correlated with prognosis, chemoresistance, and immune infiltration in pancreatic adenocarcinoma: a preliminary study based on bioinformatics analysis. Curr Oncol 2023; 30: 2997-3019. doi: 10.3390/curroncol30030228
- Langfelder P, Horvath S. WGCNA: an R package for weighted correlation network analysis. BMC Bioinformatics 2008; 9: 559. doi: 10.1186/14712105-9-559
- Tibshirani R. The lasso method for variable selection in the Cox model. Stat Med 1997; 16: 385-95. doi: 10.1002/(sici)1097-0258(19970228)16:4<;385::aid-sim380>3.0.co;2-3
- Hidalgo M. Pancreatic cancer. N Engl J Med 2010; 362: 1605-17. doi: 10.1056/NEJMra0901557
- Von Hoff DD, Ervin T, Arena FP, Chiorean EG, Infante J, Moore M, et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med 2013; 369: 1691-703. doi: 10.1056/NEJMoa1304369
- Conroy T, Desseigne F, Ychou M, Bouché O, Guimbaud R, Bécouarn Y, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med 2011; 364: 1817-25. doi: 10.1056/NEJMoa1011923
- Couzin-Frankel J. Breakthrough of the year 2013. Cancer immunotherapy. Science 2013; 342: 1432-3. doi: 10.1126/science.342.6165.1432
- Kumar A, Swain CA, Shevde LA. Informing the new developments and future of cancer immunotherapy: future of cancer immunotherapy. Cancer Metastasis Rev 2021; 40: 549-62. doi: 10.1007/s10555-021-09967-1
- Morrison AH, Byrne KT, Vonderheide RH. Immunotherapy and prevention of pancreatic cancer. Trends Cancer 2018; 4: 418-28. doi: 10.1016/j. trecan.2018.04.001
- Yin C, Alqahtani A, Noel MS. The next frontier in pancreatic cancer: targeting the tumor immune milieu and molecular pathways. Cancers 2022; 14: 2619. doi: 10.3390/cancers14112619
- Li F, He C, Yao H, Liang W, Ye X, Ruan J, et al. GLUT1 regulates the tumor immune microenvironment and promotes tumor metastasis in pancreatic adenocarcinoma via ncRNA-mediated network. J Cancer 2022; 13: 2540-58. doi: 10.7150/jca.72161
- Garrido-Laguna I, Hidalgo M. Pancreatic cancer: from state-of-the-art treatments to promising novel therapies. Nat Rev Clin Oncol 2015; 12: 319-334. doi: 10.1038/nrclinonc.2015.53
- Tong X, Tang R, Xiao M, Xu J, Wang W, Zhang B, et al. Targeting cell death pathways for cancer therapy: recent developments in necroptosis, pyroptosis, ferroptosis, and cuproptosis research. J Hematol Oncol 2022; 15: 174. doi: 10.1186/s13045-022-01392-3
- Qin Y, Liu Y, Xiang X, Long X, Chen Z, Huang X, et al. Cuproptosis correlates with immunosuppressive tumor microenvironment based on pan-cancer multiomics and single-cell sequencing analysis. Mol Cancer 2023; 22: 59. doi: 10.1186/s12943-023-01752-8
- Guo B, Yang F, Zhang L, Zhao Q, Wang W, Yin L, et al. Cuproptosis induced by ROS responsive nanoparticles with elesclomol and copper combined with αPD-L1 for enhanced cancer immunotherapy. Adv Mater 2023; 35: e2212267. doi: 10.1002/adma.202212267
- Liu WQ, Lin WR, Yan L, Xu WH, Yang J. Copper homeostasis and cuproptosis in cancer immunity and therapy. Immunol Rev 2024; 321: 211-27. doi: 10.1111/imr.13276
- Li J, Yin J, Li W, Wang H, Ni B. Molecular subtypes based on cuproptosis-related genes and tumor microenvironment infiltration characteristics in pancreatic adenocarcinoma. Cancer Cell Int 2023; 23: 7. doi: 10.1186/s12935-022-02836-z
- Wang G, Chen B, Su Y, Qu N, Zhou D, Zhou W. CEP55 as a promising immune intervention marker to regulate tumor progression: a pan-cancer analysis with experimental verification. Cells 2023; 12: 2457. doi: 10.3390/cells12202457
- Neuzillet C, Tijeras-Raballand A, Ragulan C, Cros J, Patil Y, Martinet M, et al. State of the art and future directions of pancreatic ductal adenocarcinoma therapy. Pharmacol Ther 2015; 155: 80-104. doi: 10.1016/j. pharmthera.2015.08.006
- Xiao Y, Yu D. Tumor microenvironment as a therapeutic target in cancer. Pharmacol Ther 2021; 221: 107753. doi: 10.1016/j.pharmthera.2020.107753
- Joyce JA, Fearon DT. T cell exclusion, immune privilege, and the tumor microenvironment. Science 2015; 348: 74-80. doi: 10.1126/science.aaa6204
- Kleeff J, Beckhove P, Esposito I, Herzig S, Huber PE, Lohr JM, et al. Pancreatic cancer microenvironment. Int J Cancer 2007; 121: 699-705. doi: 10.1002/ijc.22871
- Korc M. Pancreatic cancer-associated stroma production. Am J Surg 2007; 194: S84-86. doi: 10.1016/j.amjsurg.2007.05.004
- Danaher P, Warren S, Lu R, Samayoa J, Sullivan A, Pekker I, et al. Pancancer adaptive immune resistance as defined by the Tumor Inflammation Signature (TIS): results from The Cancer Genome Atlas (TCGA). J Immunother Cancer 2018; 6: 63. doi: 10.1186/s40425-018-0370-7
- Lutz ER, Wu AA, Bigelow E, Sharma R, Mo G, Soares K, et al. Immunotherapy converts nonimmunogenic pancreatic tumors into immunogenic foci of immune regulation. Cancer Immunol Res 2014; 2: 616-31. doi: 10.1158/2326-6066.CIR-14-0027
- J Gunderson A, Rajamanickam V, Bui C, Bernard B, Pucilowska J, Ballesteros-Merino C, et al. Germinal center reactions in tertiary lymphoid structures associate with neoantigen burden, humoral immunity and long-term survivorship in pancreatic cancer. Oncoimmunology 2021; 10: 1900635. doi: 10.1080/2162402x.2021.1900635
- Tang R, Zhang Y, Liang C, Xu J, Meng Q, Hua J, et al. The role of m6A-related genes in the prognosis and immune microenvironment of pancreatic adenocarcinoma. PeerJ 2020; 8: e9602. doi: 10.7717/peerj.9602
- Wang L, Zhang S, Li H, Xu Y, Wu Q, Shen J, et al. Quantification of m6A RNA methylation modulators pattern was a potential biomarker for prognosis and associated with tumor immune microenvironment of pancreatic adenocarcinoma. BMC Cancer 2021; 21: 876. doi: 10.1186/s12885-021-08550-9
- Wang G, Yang L, Gao J, Mu H, Song Y, Jiang X, et al. Identification of candidate biomarker ASXL2 and its predictive value in pancreatic carcinoma. Front Oncol 2021; 11: 736694. doi: 10.3389/fonc.2021.736694
- Lestari B, Utomo RY. CEP55 inhibitor: Extensive computational approach defining a new target of cell cycle machinery agent. Adv Pharm Bull 2022; 12: 191-99. doi: 10.34172/apb.2022.021
- Kalimutho M, Sinha D, Jeffery J, Nones K, Srihari S, Fernando WC, et al. CEP55 is a determinant of cell fate during perturbed mitosis in breast cancer. EMBO Mol Med 2018; 10: e8566. doi: 10.15252/emmm.201708566
- Sinha D, Nag P, Nanayakkara D, Duijf PHG, Burgess A, Raninga P, et al. Cep55 overexpression promotes genomic instability and tumorigenesis in mice. Commun Biol 2020; 3: 593. doi: 10.1038/s42003-020-01304-6
- Zhang X, Xu Q, Li E, Shi T, Chen H. CEP55 predicts the poor prognosis and promotes tumorigenesis in endometrial cancer by regulating the Foxo1 signaling. Mol Cell Biochem 2023; 478: 1561-71. doi: 10.1007/s11010-022-04607-w
- Ye Y, Chen Z, Shen Y, Qin Y, Wang H. Development and validation of a fourlipid metabolism gene signature for diagnosis of pancreatic cancer. FEBS Open Bio 2021; 11: 3153-70. doi: 10.1002/2211-5463.13074
- Luo X, Linghu M, Zhou X, Ru Y, Huang Q, Liu D, et al. Merestinib inhibits cuproptosis by targeting NRF2 to alleviate acute liver injury. Free Radic Biol Med 2025; 229: 68-81. doi: 10.1016/j.freeradbiomed.2025.01.029
Language: English
Page range: 368 - 382
Submitted on: Jan 21, 2025
Accepted on: Apr 26, 2025
Published on: Jul 18, 2025
Published by: Association of Radiology and Oncology
In partnership with: Paradigm Publishing Services
Publication frequency: 4 issues per year
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© 2025 Riyuan Zhang, Zixia Xu, Yurui Zhuang, Yuzhe Shi, Ziyi Guo, Chong Chen, published by Association of Radiology and Oncology
This work is licensed under the Creative Commons Attribution 4.0 License.