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BMC Urology

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Open Access 01-12-2023 | Urothelial Cancer | Research

Comprehensive analysis of cuproptosis-related lncRNAs signature to predict prognosis in bladder urothelial carcinoma

Authors: Shusheng Zhu, Houying Li, Yanpeng Fan, Chao Tang

Published in: BMC Urology | Issue 1/2023

Abstract

Background

Cuproptosis-related genes (CRGs) have been recently discovered to regulate the occurrence and development of various tumors by controlling cuproptosis, a novel type of copper ion-dependent cell death. Although cuproptosis is mediated by lipoylated tricarboxylic acid cycle proteins, the relationship between cuproptosis-related long noncoding RNAs (crlncRNAs) in bladder urothelial carcinoma (BLCA) and clinical outcomes, tumor microenvironment (TME) modification, and immunotherapy remains unknown. In this paper, we tried to discover the importance of lncRNAs for BLCA.

Methods

The BLCA-related lncRNAs and clinical data were first obtained from The Cancer Genome Atlas (TCGA). CRGs were obtained through Coexpression, Cox regression and Lasso regression. Besides, a prognosis model was established for verification. Meanwhile, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, gene ontology (GO) analysis, principal component analysis (PCA), half-maximal inhibitory concentration prediction (IC50), immune status and drug susceptibility analysis were carried out.

Results

We identified 277 crlncRNAs and 16 survival-related lncRNAs. According to the 8-crlncRNA risk model, patients could be divided into high-risk group and low-risk group. Progression-Free-Survival (PFS), independent prognostic analysis, concordance index (C-index), receiver operating characteristic (ROC) curve and nomogram all confirmed the excellent predictive capability of the 8-lncRNA risk model for BLCA. During gene mutation burden survival analysis, noticeable differences were observed in high- and low-risk patients. We also found that the two groups of patients might respond differently to immune targets and anti-tumor drugs.

Conclusion

The nomogram with 8-lncRNA may help guide treatment of BLCA. More clinical studies are necessary to verify the nomogram.

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Siegel RL, Miller KD, Fuchs HE, Cancer, Statistics, et al. 2021 CA Cancer J Clin. 2021;71(1):7–33. https://doi.org/10.3322/caac.21654.CrossRefPubMed

Richters A, Aben KKH, Kiemeney L. The global burden of urinary bladder cancer: an update. World J Urol. 2020;38(8):1895–904. https://doi.org/10.1007/s00345-019-02984-4.CrossRefPubMed

Cambier S, Sylvester RJ, Collette L, et al. EORTC Nomograms and Risk Groups for Predicting recurrence, progression, and Disease-specific and overall survival in Non-Muscle-invasive Stage Ta-T1 urothelial bladder Cancer patients treated with 1–3 years of maintenance Bacillus Calmette-Guerin. Eur Urol. 2016;69(1):60–9. https://doi.org/10.1016/j.eururo.2015.06.045.CrossRefPubMed

Zhang Y, Li X, Li X, et al. Comprehensive analysis of cuproptosis-related long noncoding RNA immune infiltration and prediction of prognosis in patients with bladder cancer. Front Genet. 2022;13:990326. https://doi.org/10.3389/fgene.2022.990326.CrossRefPubMedPubMedCentral

Andreini C, Banci L, Bertini I, et al. Counting the zinc-proteins encoded in the human genome. J Proteome Res. 2006;5(1):196–201. https://doi.org/10.1021/pr050361j.CrossRefPubMed

Kim BE, Nevitt T, Thiele DJ. Mechanisms for copper acquisition, distribution and regulation. Nat Chem Biol. 2008;4(3):176–85. https://doi.org/10.1038/nchembio.72.CrossRefPubMed

Festa RA, Thiele DJ. Copper: an essential metal in biology. Curr Biol. 2011;21(21):R877–883. https://doi.org/10.1016/j.cub.2011.09.040.CrossRefPubMedPubMedCentral

Cobine PA, Moore SA, Leary SC. Getting out what you put in: copper in mitochondria and its impacts on human disease. Biochim Biophys Acta Mol Cell Res. 2021;1868(1):118867. https://doi.org/10.1016/j.bbamcr.2020.118867.CrossRefPubMed

Brady DC, Crowe MS, Turski ML et al. Copper is required for oncogenic BRAF signalling and tumorigenesis.Nature.2014;509(7501):492–6. doi:https://doi.org/10.1038/nature13180.

10.

Tsang T, Posimo JM, Gudiel AA, et al. Copper is an essential regulator of the autophagic kinases ULK1/2 to drive lung adenocarcinoma. Nat Cell Biol. 2020;22(4):412–24. https://doi.org/10.1038/s41556-020-0481-4.CrossRefPubMedPubMedCentral

11.

Li SR, Bu LL, Cai L. Cuproptosis: lipoylated TCA cycle proteins-mediated novel cell death pathway. Signal Transduct Target Ther. 2022;7(1):158. https://doi.org/10.1038/s41392-022-01014-x.CrossRefPubMedPubMedCentral

12.

Tsvetkov P, Coy S, Petrova B, et al. Copper induces cell death by targeting lipoylated. TCA cycle proteins Science. 2022;375(6586):1254–61. https://doi.org/10.1126/science.abf0529.CrossRefPubMed

13.

Yu W, Huo H, You Z, et al. Identification of cuproptosis-associated IncRNAs signature and establishment of a novel nomogram for prognosis of stomach adenocarcinoma. Front Genet. 2022;13:982888. https://doi.org/10.3389/fgene.2022.982888.CrossRefPubMedPubMedCentral

14.

Quinn JJ, Chang HY. Unique features of long non-coding RNA biogenesis and function. Nat Rev Genet. 2016;17(1):47–62. https://doi.org/10.1038/nrg.2015.10.CrossRefPubMed

15.

Yang J, Liu F, Wang Y, et al. LncRNAs in tumor metabolic reprogramming and immune microenvironment remodeling. Cancer Lett. 2022;543:215798. https://doi.org/10.1016/j.canlet.2022.215798.CrossRefPubMed

16.

Huang Q, Yan J, Agami R. Long non-coding RNAs in metastasis. Cancer Metastasis Rev. 2018;37(1):75–81. https://doi.org/10.1007/s10555-017-9713-x.CrossRefPubMed

17.

Zhao Z, Liu H, Zhou X, et al. Necroptosis-related lncRNAs: Predicting Prognosis and the distinction between the Cold and Hot Tumors in gastric Cancer. J Oncol. 2021;2021:6718443. https://doi.org/10.1155/2021/6718443.CrossRefPubMedPubMedCentral

18.

Meng T, Huang R, Zeng Z, et al. Identification of prognostic and metastatic alternative splicing signatures in kidney renal clear cell carcinoma. Front Bioeng Biotechnol. 2019;7:270. https://doi.org/10.3389/fbioe.2019.00270.CrossRefPubMedPubMedCentral

19.

Jiang P, Gu S, Pan D, et al. Signatures of T cell dysfunction and exclusion predict cancer immunotherapy response. Nat Med. 2018;24(10):1550–8. https://doi.org/10.1038/s41591-018-0136-1.CrossRefPubMedPubMedCentral

20.

Yang L, Yu J, Tao L, et al. Cuproptosis-related lncRNAs are biomarkers of prognosis and Immune Microenvironment in Head and Neck squamous cell carcinoma. Front Genet. 2022;13:947551. https://doi.org/10.3389/fgene.2022.947551.CrossRefPubMedPubMedCentral

21.

Geeleher P, Cox NJ, Huang RS. Clinical drug response can be predicted using baseline gene expression levels and in vitro drug sensitivity in cell lines. Genome Biol. 2014;15(3):R47. https://doi.org/10.1186/gb-2014-15-3-r47.CrossRefPubMedPubMedCentral

22.

Kanehisa M, Goto SKEGG. : kyoto encyclopedia of genes and genomes. Nucleic Acids Res. 2000;28(1):27–30. https://doi.org/10.1093/nar/28.1.27.CrossRefPubMedPubMedCentral

23.

Kanehisa M. Toward understanding the origin and evolution of cellular organisms. Protein Sci. 2019;28(11):1947–51. https://doi.org/10.1002/pro.3715.CrossRefPubMedPubMedCentral

24.

Kanehisa M, Furumichi M, Sato Y, et al. KEGG for taxonomy-based analysis of pathways and genomes. Nucleic Acids Res. 2023;51(D1):D587–92. https://doi.org/10.1093/nar/gkac963.CrossRefPubMed

25.

Zhu K, Liu X, Deng W et al. Identification of a chromatin regulator signature and potential candidate drugs for bladder cancer.Hereditas.2022;159(1):13. doi:https://doi.org/10.1186/s41065-021-00212-x.

26.

Shi ZD, Hao L, Han XX, et al. Targeting HNRNPU to overcome cisplatin resistance in bladder cancer. Mol Cancer. 2022;21(1):37. https://doi.org/10.1186/s12943-022-01517-9.CrossRefPubMedPubMedCentral

27.

Gao Y, Shang S, Guo S, et al. Acids Res. 2021;49(D1):D1251–8. https://doi.org/10.1093/nar/gkaa1006. Lnc2Cancer 3.0: an updated resource for experimentally supported lncRNA/circRNA cancer associations and web tools based on RNA-seq and scRNA-seq data.Nucleic.

28.

Tan YT, Lin JF, Li T, et al. LncRNA-mediated posttranslational modifications and reprogramming of energy metabolism in cancer. Cancer Commun (Lond). 2021;41(2):109–20. https://doi.org/10.1002/cac2.12108.CrossRefPubMed

29.

Zhang C, Wang W, Lin J, et al. lncRNA CCAT1 promotes bladder cancer cell proliferation, migration and invasion.Int. Braz J Urol. 2019;45(3):549–59. https://doi.org/10.1590/S1677-5538.IBJU.2018.0450.CrossRef

30.

Luo H, Xu C, Le W, et al. lncRNA CASC11 promotes cancer cell proliferation in bladder cancer through miRNA-150. J Cell Biochem. 2019;120(8):13487–93. https://doi.org/10.1002/jcb.28622.CrossRefPubMedPubMedCentral

31.

Logotheti S, Marquardt S, Gupta SK et al. LncRNA-SLC16A1-AS1 induces metabolic reprogramming during bladder Cancer progression as target and co-activator of E2F1.Theranostics.2020;10(21):9620–43. doi:https://doi.org/10.7150/thno.44176.

32.

Ding W, Ling Y, Shi Y, et al. DesA prognostic risk model of LncRNAs in patients with Acute myeloid leukaemia based on TCGA Data. Front Bioeng Biotechnol. 2022;10:818905. https://doi.org/10.3389/fbioe.2022.818905.CrossRefPubMedPubMedCentral

33.

Lin L, Fang T, Lin L, et al. Genetic variants relate to Fasting plasma glucose, 2-Hour postprandial glucose, glycosylated hemoglobin, and BMI in Prediabetes. Front Endocrinol (Lausanne). 2022;13:778069. https://doi.org/10.3389/fendo.2022.778069.CrossRefPubMed

34.

Sun Z, Jing C, Xiao C, et al. An autophagy-related long non-coding RNA prognostic signature accurately predicts survival outcomes in bladder urothelial carcinoma patients.Aging. (Albany NY). 2020;12(15):15624–37. https://doi.org/10.18632/aging.103718.CrossRef

35.

Sun X, Qian Y, Wang X, et al. LncRNA TRG-AS1 stimulates hepatocellular carcinoma progression by sponging miR-4500 to modulate BACH1. Cancer Cell Int. 2020;20:367. https://doi.org/10.1186/s12935-020-01440-3.CrossRefPubMedPubMedCentral

36.

Zhang M, Zhu W, Haeryfar M, et al. Long non-coding RNA TRG-AS1 promoted Proliferation and Invasion of Lung Cancer cells through the miR-224-5p/SMAD4 Axis. Onco Targets Ther. 2021;14:4415–26. https://doi.org/10.2147/OTT.S297336.CrossRefPubMedPubMedCentral

37.

Xie H, Shi S, Chen Q, et al. LncRNA TRG-AS1 promotes glioblastoma cell proliferation by competitively binding with mir-877-5p to regulate SUZ12 expression. Pathol Res Pract. 2019;215(8):152476. https://doi.org/10.1016/j.prp.2019.152476.CrossRefPubMed

38.

Cao R, Cui L, Zhang J, et al. Immune-related lncRNA classification of head and neck squamous cell carcinoma. Cancer Cell Int. 2022;22(1):25. https://doi.org/10.1186/s12935-022-02450-z.CrossRefPubMedPubMedCentral

39.

Zhao D, Zhao H, He Y, et al. The inhibitive effects of proteasome inhibitor MG-132 on pterygium fibroblasts in vitro and the potential key regulators involved. Life Sci. 2021;270:119088. https://doi.org/10.1016/j.lfs.2021.119088.CrossRefPubMed

40.

Ye J, Li H, Wei J, et al. Risk Scoring System based on lncRNA expression for Predicting Survival in Hepatocellular Carcinoma with Cirrhosis.Asian Pac. J Cancer Prev. 2020;21(6):1787–95. https://doi.org/10.31557/APJCP.2020.21.6.1787.CrossRef

41.

LoRusso PM. Inhibition of the PI3K/AKT/mTOR pathway in solid tumors. J Clin Oncol. 2016;34(31):3803–15. https://doi.org/10.1200/JCO.2014.59.0018.CrossRefPubMedPubMedCentral

42.

Correa H, Li-Fraumeni. Syndrome J Pediatr Genet. 2016;5(2):84–8. https://doi.org/10.1055/s-0036-1579759.CrossRefPubMed

Title: Comprehensive analysis of cuproptosis-related lncRNAs signature to predict prognosis in bladder urothelial carcinoma
Authors: Shusheng Zhu
Houying Li
Yanpeng Fan
Chao Tang
Publication date: 01-12-2023
Publisher: BioMed Central
Keywords: Urothelial Cancer
Urothelial Cancer
Published in: BMC Urology / Issue 1/2023
Electronic ISSN: 1471-2490
DOI: https://doi.org/10.1186/s12894-023-01292-9

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Comprehensive analysis of cuproptosis-related lncRNAs signature to predict prognosis in bladder urothelial carcinoma

Abstract

Background

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

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