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Clinical and Translational Oncology

04.05.2024 | Research Article

The cuproptosis-related gene UBE2D2 functions as an immunotherapeutic and prognostic biomarker in pan-cancer

verfasst von: Yao Fei, Danping Cao, Runyu Dong, Yanna Li, Zhixiong Wang, Peng Gao, Menglin Zhu, Xiaoming Wang, Xueliang Zuo, Juan Cai

Erschienen in: Clinical and Translational Oncology

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Abstract

Background

Cuproptosis, as a unique modality of regulated cell death, requires the involvement of ubiquitin-binding enzyme UBE2D2. However, the prognostic and immunotherapeutic values of UBE2D2 in pan-cancer remain largely unknown.

Methods

Using UCSC Xena, TIMER, Clinical Proteomic Tumor Analysis Consortium (CPTAC), and Human Protein Atlas (HPA) databases, we aimed to explore the differential expression pattern of UBE2D2 across multiple cancer types and to evaluate its association with patient prognosis, clinical features, and genetic variations. The association between UBE2D2 and immunotherapy response was assessed by gene set enrichment analysis, tumor microenvironment, immune gene co-expression and drug half maximal inhibitory concentration (IC50) analysis.

Results

The mRNA and protein levels of UBE2D2 were markedly elevated in most cancer types, and UBE2D2 exhibited prognostic significance in liver hepatocellular carcinoma (LIHC), kidney chromophobe (KICH), uveal melanomas (UVM), cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC), and kidney renal papillary cell carcinoma (KIRP). UBE2D2 expression was correlated with clinical features, tumor mutation burden, microsatellite instability, and anti-tumor drug resistance in several tumor types. Gene enrichment analysis showed that UBE2D2 was significantly associated with immune-related pathways. The expression level of UBE2D2 was correlated with immune cell infiltration, including CD4 + T cells、Macrophages M2、CD8 + T cells in pan-cancer. PDCD1, CD274 and CTLA4 expression levels were positively correlated with UBE2D2 level in multiple cancers.

Conclusions

We comprehensively investigated the potential value of UBE2D2 as a prognostic and immunotherapeutic predictor for pan-cancer, providing a novel insight for cancer immunotherapy.
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Literatur
1.
Torre LA, Siegel RL, Ward EM, Jemal A. Global cancer incidence and mortality rates and trends–an update. Cancer Epidemiol Biomarkers Prev. 2016;25:16–27.PubMedCrossRef
2.
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.PubMedPubMedCentralCrossRef
3.
4.
Cui L, Gouw AM, LaGory EL, Guo S, Attarwala N, Tang Y, et al. Mitochondrial copper depletion suppresses triple-negative breast cancer in mice. Nat Biotechnol. 2021;39:357–67.PubMedCrossRef
5.
Ramchandani D, Berisa M, Tavarez DA, Li Z, Miele M, Bai Y, et al. Copper depletion modulates mitochondrial oxidative phosphorylation to impair triple negative breast cancer metastasis. Nat Commun. 2021;12:7311.PubMedPubMedCentralCrossRef
6.
Liao Y, Zhao J, Bulek K, Tang F, Chen X, Cai G, et al. Inflammation mobilizes copper metabolism to promote colon tumorigenesis via an IL-17-STEAP4-XIAP axis. Nat Commun. 2020;11:900.PubMedPubMedCentralCrossRef
7.
Wang J, Qin D, Tao Z, Wang B, Xie Y, Wang Y, et al. Identification of cuproptosis-related subtypes, construction of a prognosis model, and tumor microenvironment landscape in gastric cancer. Front Immunol. 2022;13:1056932.PubMedPubMedCentralCrossRef
8.
9.
Kazi Tani LS, Gourlan AT, Dennouni-Medjati N, Telouk P, Dali-Sahi M, Harek Y, et al. Copper isotopes and copper to zinc ratio as possible biomarkers for thyroid cancer. Front Med. 2021;8: 698167.CrossRef
10.
Ge EJ, Bush AI, Casini A, Cobine PA, Cross JR, DeNicola GM, et al. Connecting copper and cancer: from transition metal signalling to metalloplasia. Nat Rev Cancer. 2022;22:102–13.PubMedCrossRef
11.
Huang Y, Yin D, Wu L. Identification of cuproptosis-related subtypes and development of a prognostic signature in colorectal cancer. Sci Rep. 2022;12:17348.PubMedPubMedCentralCrossRef
12.
Cockram PE, Kist M, Prakash S, Chen SH, Wertz IE, Vucic D. Ubiquitination in the regulation of inflammatory cell death and cancer. Cell Death Differ. 2021;28:591–605.PubMedPubMedCentralCrossRef
13.
Lipkowitz S, Weissman AM. RINGs of good and evil: RING finger ubiquitin ligases at the crossroads of tumour suppression and oncogenesis. Nat Rev Cancer. 2011;11:629–43.PubMedPubMedCentralCrossRef
14.
Goldman MJ, Craft B, Hastie M, Repečka K, McDade F, Kamath A, et al. Visualizing and interpreting cancer genomics data via the Xena platform. Nat Biotechnol. 2020;38:675–8.PubMedPubMedCentralCrossRef
15.
Li T, Fu J, Zeng Z, Cohen D, Li J, Chen Q, et al. TIMER2.0 for analysis of tumor-infiltrating immune cells. Nucleic Acids Res. 2020;48:W509–14.PubMedPubMedCentralCrossRef
16.
Edwards NJ, Oberti M, Thangudu RR, Cai S, McGarvey PB, Jacob S, et al. The CPTAC data portal: a resource for cancer proteomics research. J Proteome Res. 2015;14:2707–13.PubMedCrossRef
17.
Chandrashekar DS, Karthikeyan SK, Korla PK, Patel H, Shovon AR, Athar M, et al. UALCAN: an update to the integrated cancer data analysis platform. Neoplasia. 2022;25:18–27.PubMedPubMedCentralCrossRef
18.
Colwill K, Gräslund S. A roadmap to generate renewable protein binders to the human proteome. Nat Methods. 2011;8:551–8.PubMedCrossRef
19.
Gao J, Aksoy BA, Dogrusoz U, Dresdner G, Gross B, Sumer SO, et al. Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal. Sci Signal. 2013;6:pl1.CrossRefPubMedPubMedCentral
20.
21.
22.
Schober P, Boer C, Schwarte LA. Correlation coefficients: appropriate use and Interpretation. Anesth Analg. 2018;126:1763–8.PubMedCrossRef
23.
Yoshihara K, Shahmoradgoli M, Martínez E, Vegesna R, Kim H, Torres-Garcia W, et al. Inferring tumour purity and stromal and immune cell admixture from expression data. Nat Commun. 2013;4:2612.PubMedCrossRef
24.
Newman AM, Liu CL, Green MR, Gentles AJ, Feng W, Xu Y, et al. Robust enumeration of cell subsets from tissue expression profiles. Nat Methods. 2015;12:453–7.PubMedPubMedCentralCrossRef
25.
Shankavaram UT, Varma S, Kane D, Sunshine M, Chary KK, Reinhold WC, et al. Cell Miner: a relational database and query tool for the NCI-60 cancer cell lines. BMC Genomics. 2009;10:277.PubMedPubMedCentralCrossRef
26.
Luchini C, Bibeau F, Ligtenberg MJL, Singh N, Nottegar A, Bosse T, et al. ESMO recommendations on microsatellite instability testing for immunotherapy in cancer, and its relationship with PD-1/PD-L1 expression and tumour mutational burden: a systematic review-based approach. Ann Oncol. 2019;30:1232–43.PubMedCrossRef
27.
Rizzo A, Ricci AD, Brandi G. PD-L1, TMB, MSI, and other predictors of response to immune checkpoint inhibitors in biliary tract cancer. Cancers. 2021;13:558.CrossRefPubMedPubMedCentral
28.
Condelli V, Calice G, Cassano A, Basso M, Rodriquenz MG, Zupa A, et al. Novel epigenetic eight-gene signature predictive of poor prognosis and MSI-like phenotype in human metastatic colorectal carcinomas. Cancers. 2021;13:158.CrossRefPubMedPubMedCentral
29.
30.
31.
32.
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.PubMedPubMedCentralCrossRef
33.
Li J, Wu F, Li C, Sun S, Feng C, Wu H, et al. The cuproptosis-related signature predicts prognosis and indicates immune microenvironment in breast cancer. Front Genet. 2022;13: 977322.PubMedPubMedCentralCrossRef
34.
Winkler GS, Albert TK, Dominguez C, Legtenberg YI, Boelens R, Timmers HT. An altered-specificity ubiquitin-conjugating enzyme/ubiquitin-protein ligase pair. J Mol Biol. 2004;337:157–65.PubMedCrossRef
35.
Gonen H, Bercovich B, Orian A, Carrano A, Takizawa C, Yamanaka K, et al. Identification of the ubiquitin carrier proteins, E2s, involved in signal-induced conjugation and subsequent degradation of IkappaBalpha. J Biol Chem. 1999;274:14823–30.PubMedCrossRef
36.
Chiang MH, Chen LF, Chen H. Ubiquitin-conjugating enzyme UBE2D2 is responsible for FBXW2 (F-box and WD repeat domain containing 2)-mediated human GCM1 (glial cell missing homolog 1) ubiquitination and degradation. Biol Reprod. 2008;79:914–20.PubMedCrossRef
37.
Ryan PE, Sivadasan-Nair N, Nau MM, Nicholas S, Lipkowitz S. The N terminus of Cbl-c regulates ubiquitin ligase activity by modulating affinity for the ubiquitin-conjugating enzyme. J Biol Chem. 2010;285:23687–98.PubMedPubMedCentralCrossRef
38.
Smith J, Sen S, Weeks RJ, Eccles MR, Chatterjee A. Promoter DNA hypermethylation and paradoxical gene activation. Trends Cancer. 2020;6:392–406.PubMedCrossRef
39.
40.
41.
42.
Mittal V. Epithelial mesenchymal transition in tumor metastasis. Annu Rev Pathol. 2018;13:395–412.PubMedCrossRef
43.
Monteith GR, Prevarskaya N, Roberts-Thomson SJ. The calcium-cancer signalling nexus. Nat Rev Cancer. 2017;17:367–80.PubMedCrossRef
44.
45.
Liu J, Peng Y, Wei W. Cell cycle on the crossroad of tumorigenesis and cancer therapy. Trends Cell Biol. 2022;32:30–44.PubMedCrossRef
46.
47.
Ashton TM, McKenna WG, Kunz-Schughart LA, Higgins GS. Oxidative phosphorylation as an emerging target in cancer therapy. Clin Cancer Res. 2018;24:2482–90.PubMedCrossRef
48.
Dongre A, Weinberg RA. New insights into the mechanisms of epithelial-mesenchymal transition and implications for cancer. Nat Rev Mol Cell Biol. 2019;20:69–84.PubMedCrossRef
49.
Du W, Frankel TL, Green M, Zou W. IFNgamma signaling integrity in colorectal cancer immunity and immunotherapy. Cell Mol Immunol. 2022;19:23–32.PubMedCrossRef
50.
Kwon J, Bakhoum SF. The cytosolic DNA-sensing cGAS-STING pathway in cancer. Cancer Discov. 2020;10:26–39.PubMedCrossRef
51.
Jhunjhunwala S, Hammer C, Delamarre L. Antigen presentation in cancer: insights into tumour immunogenicity and immune evasion. Nat Rev Cancer. 2021;21:298–312.PubMedCrossRef
52.
Xun Y, Yang H, Kaminska B, You H. Toll-like receptors and toll-like receptor-targeted immunotherapy against glioma. J Hematol Oncol. 2021;14:176.PubMedPubMedCentralCrossRef
53.
Jiang Y, Zhang H, Wang J, Chen J, Guo Z, Liu Y, et al. Exploiting RIG-I-like receptor pathway for cancer immunotherapy. J Hematol Oncol. 2023;16:8.PubMedPubMedCentralCrossRef
54.
Yu T, Guo F, Yu Y, Sun T, Ma D, Han J, et al. Fusobacterium nucleatum promotes chemoresistance to colorectal cancer by modulating autophagy. Cell. 2017;170(548–63): e16.
55.
Zhang F, Wang H, Yu J, Yao X, Yang S, Li W, et al. LncRNA CRNDE attenuates chemoresistance in gastric cancer via SRSF6-regulated alternative splicing of PICALM. Mol Cancer. 2021;20:6.PubMedPubMedCentralCrossRef
56.
57.
Propper DJ, Balkwill FR. Harnessing cytokines and chemokines for cancer therapy. Nat Rev Clin Oncol. 2022;19:237–53.PubMedCrossRef
58.
Lei X, Lei Y, Li JK, Du WX, Li RG, Yang J, et al. Immune cells within the tumor microenvironment: Biological functions and roles in cancer immunotherapy. Cancer Lett. 2020;470:126–33.PubMedCrossRef
59.
Lee YS, Radford KJ. The role of dendritic cells in cancer. Int Rev Cell Mol Biol. 2019;348:123–78.PubMedCrossRef
60.
61.
Yoshitomi H, Ueno H. Shared and distinct roles of T peripheral helper and T follicular helper cells in human diseases. Cell Mol Immunol. 2021;18:523–7.PubMedCrossRef
62.
Wang Y, Wang C, Qiu J, Qu X, Peng J, Lu C, et al. Targeting CD96 overcomes PD-1 blockade resistance by enhancing CD8+ TIL function in cervical cancer. J Immunother Cancer. 2022;10:e003667.
63.
64.
Mendhiratta N, Muraki P, Sisk AE Jr, Shuch B. Papillary renal cell carcinoma: review. Urol Oncol. 2021;39:327–37.PubMedCrossRef
Metadaten
Titel
The cuproptosis-related gene UBE2D2 functions as an immunotherapeutic and prognostic biomarker in pan-cancer
verfasst von
Yao Fei
Danping Cao
Runyu Dong
Yanna Li
Zhixiong Wang
Peng Gao
Menglin Zhu
Xiaoming Wang
Xueliang Zuo
Juan Cai
Publikationsdatum
04.05.2024
Verlag
Springer International Publishing
Erschienen in
Clinical and Translational Oncology
Print ISSN: 1699-048X
Elektronische ISSN: 1699-3055
DOI
https://doi.org/10.1007/s12094-024-03495-4

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