A Signature of Cuproptosis-related LncRNAs Predicts Prognosis and Provides Basis for Future Anti-tumor Drug Development in Breast Cancer

Overview

Journal Transl Cancer Res

Specialty Oncology

Date 2023 Jul 12

PMID 37434691

Authors

Hao Yu

Yanbiao Liu

Wenrong Zhang

Ziqi Peng

Xinmiao Yu

Feng Jin

Affiliations

Soon will be listed here.

Abstract

Background: Breast cancer is the most prevalent malignancy worldwide and the leading culprit for women's death. Cuproptosis is a novel and promising modality of tumor cell death and the relationship with long non-coding RNAs (lncRNAs) remains shrouded in a veil. Studies in cuproptosis-related lncRNAs can aid in the clinical management of breast cancer and provide a basis for anti-tumor drug development.

Methods: RNA-Seq data, somatic mutation data, and clinical information were downloaded from The Cancer Genome Atlas (TCGA). Patients were divided into high- and low-risk groups according to the risk score. Cox regression and least absolute shrinkage and selection operator (LASSO) regression analyses were used to select prognostic lncRNAs to construct a risk score system. Its' prognostic value was confirmed in the training and validation cohorts subsequently. Functional analysis regarding cuproptosis-related lncRNAs was performed.

Results: Eighteen cuproptosis-related lncRNAs were identified and 11 of them including , , , , , , , , , and were selected for risk score system construction. The risk score was confirmed as an independent prognostic factor and patients in the high-risk group had a worse prognosis. A nomogram based on the independent prognostic factors was constructed for clinical decision aids. Further analyses revealed that patients in the high-risk group faced a heavier tumor mutational burden (TMB) and suppressed anti-tumor immunity. Besides, cuproptosis-related lncRNAs were associated with the expression of immune checkpoint inhibitors, N6-adenylate methylation (m6a), and drug sensitivity in breast cancer.

Conclusions: A prognostic risk score system with satisfactory predictive accuracy was constructed. Besides, cuproptosis-related lncRNAs can influence the immune microenvironment, TMB, m6a, and drug sensitivity in breast cancer, which may provide a basis for future anti-tumor drug development.

Citing Articles

OTUD6B-AS1: a multifaceted regulator of cancer with critical clinical implications.

Zheng Z, Zhou C, Yi F, Li J Am J Cancer Res. 2025; 15(1):1-18.

PMID: 39949926 PMC: 11815388. DOI: 10.62347/EHQK5961.

Establishment and verification of a prognostic immune cell signature-based model for breast cancer overall survival.

Liu H, Bao H, Zhao J, Zhu F, Zheng C Transl Cancer Res. 2024; 13(10):5600-5615.

PMID: 39525032 PMC: 11543049. DOI: 10.21037/tcr-24-1829.

lncRNAs as prognostic markers and therapeutic targets in cuproptosis-mediated cancer.

Bhat A, Afzal M, Moglad E, Thapa R, Ali H, Almalki W Clin Exp Med. 2024; 24(1):226.

PMID: 39325172 PMC: 11427524. DOI: 10.1007/s10238-024-01491-0.

Elucidating the evolving role of cuproptosis in breast cancer progression.

Zhu Z, Zhu K, Zhang J, Zhou Y, Zhang Q Int J Biol Sci. 2024; 20(12):4872-4887.

PMID: 39309446 PMC: 11414396. DOI: 10.7150/ijbs.98806.

References

Yan H, Luo B, Wu X, Guan F, Yu X, Zhao L . Cisplatin Induces Pyroptosis via Activation of MEG3/NLRP3/caspase-1/GSDMD Pathway in Triple-Negative Breast Cancer. Int J Biol Sci. 2021; 17(10):2606-2621. PMC: 8315016. DOI: 10.7150/ijbs.60292. View

Li P, Li R, Huang Y, Lu J, Zhang W, Wang Z . LncRNA OTUD6B-AS1 promotes paclitaxel resistance in triple negative breast cancer by regulation of miR-26a-5p/MTDH pathway-mediated autophagy and genomic instability. Aging (Albany NY). 2021; 13(21):24171-24191. PMC: 8610138. DOI: 10.18632/aging.203672. View

Ullah M . Breast Cancer: Current Perspectives on the Disease Status. Adv Exp Med Biol. 2019; 1152:51-64. DOI: 10.1007/978-3-030-20301-6_4. View

Zhao W, Geng D, Li S, Chen Z, Sun M . LncRNA HOTAIR influences cell growth, migration, invasion, and apoptosis via the miR-20a-5p/HMGA2 axis in breast cancer. Cancer Med. 2018; 7(3):842-855. PMC: 5852357. DOI: 10.1002/cam4.1353. View

Wang J, Xie S, Yang J, Xiong H, Jia Y, Zhou Y . The long noncoding RNA H19 promotes tamoxifen resistance in breast cancer via autophagy. J Hematol Oncol. 2019; 12(1):81. PMC: 6657081. DOI: 10.1186/s13045-019-0747-0. View

Aich M, Chakraborty D . Role of lncRNAs in stem cell maintenance and differentiation. Curr Top Dev Biol. 2020; 138:73-112. DOI: 10.1016/bs.ctdb.2019.11.003. View

Loibl S, Poortmans P, Morrow M, Denkert C, Curigliano G . Breast cancer. Lancet. 2021; 397(10286):1750-1769. DOI: 10.1016/S0140-6736(20)32381-3. View

Dong S, Ma M, Li M, Guo Y, Zuo X, Gu X . LncRNA MEG3 regulates breast cancer proliferation and apoptosis through miR-141-3p/RBMS3 axis. Genomics. 2021; 113(4):1689-1704. DOI: 10.1016/j.ygeno.2021.04.015. View

Waks A, Winer E . Breast Cancer Treatment: A Review. JAMA. 2019; 321(3):288-300. DOI: 10.1001/jama.2018.19323. View

10.

Przanowska R, Weidmann C, Saha S, Cichewicz M, Jensen K, Przanowski P . Distinct MUNC lncRNA structural domains regulate transcription of different promyogenic factors. Cell Rep. 2022; 38(7):110361. PMC: 8937029. DOI: 10.1016/j.celrep.2022.110361. View

11.

Tsvetkov P, Coy S, Petrova B, Dreishpoon M, Verma A, Abdusamad M . Copper induces cell death by targeting lipoylated TCA cycle proteins. Science. 2022; 375(6586):1254-1261. PMC: 9273333. DOI: 10.1126/science.abf0529. View

12.

Castro F, Cardoso A, Goncalves R, Serre K, Oliveira M . Interferon-Gamma at the Crossroads of Tumor Immune Surveillance or Evasion. Front Immunol. 2018; 9:847. PMC: 5945880. DOI: 10.3389/fimmu.2018.00847. View

13.

Statello L, Guo C, Chen L, Huarte M . Gene regulation by long non-coding RNAs and its biological functions. Nat Rev Mol Cell Biol. 2020; 22(2):96-118. PMC: 7754182. DOI: 10.1038/s41580-020-00315-9. View

14.

Sung H, Ferlay J, Siegel R, Laversanne M, Soerjomataram I, Jemal A . Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021; 71(3):209-249. DOI: 10.3322/caac.21660. View

15.

Dong F, Ruan S, Wang J, Xia Y, Le K, Xiao X . M2 macrophage-induced lncRNA PCAT6 facilitates tumorigenesis and angiogenesis of triple-negative breast cancer through modulation of VEGFR2. Cell Death Dis. 2020; 11(9):728. PMC: 7481779. DOI: 10.1038/s41419-020-02926-8. View

16.

Mao C, Wang X, Liu Y, Wang M, Yan B, Jiang Y . A G3BP1-Interacting lncRNA Promotes Ferroptosis and Apoptosis in Cancer via Nuclear Sequestration of p53. Cancer Res. 2018; 78(13):3484-3496. PMC: 8073197. DOI: 10.1158/0008-5472.CAN-17-3454. View

17.

Liang Y, Zhang H, Song X, Yang Q . Metastatic heterogeneity of breast cancer: Molecular mechanism and potential therapeutic targets. Semin Cancer Biol. 2019; 60:14-27. DOI: 10.1016/j.semcancer.2019.08.012. View

18.

Verret B, Cortes J, Bachelot T, Andre F, Arnedos M . Efficacy of PI3K inhibitors in advanced breast cancer. Ann Oncol. 2019; 30(Suppl_10):x12-x20. PMC: 6923787. DOI: 10.1093/annonc/mdz381. View

19.

Kaur P, Campo D, Porras T, Ring A, Lu J, Chairez Y . A Pilot Study for the Feasibility of Exome-Sequencing in Circulating Tumor Cells Versus Single Metastatic Biopsies in Breast Cancer. Int J Mol Sci. 2020; 21(14). PMC: 7402350. DOI: 10.3390/ijms21144826. View

20.

Dave A, Charytonowicz D, Francoeur N, Beaumont M, Beaumont K, Schmidt H . The Breast Cancer Single-Cell Atlas: Defining cellular heterogeneity within model cell lines and primary tumors to inform disease subtype, stemness, and treatment options. Cell Oncol (Dordr). 2023; 46(3):603-628. PMC: 10205851. DOI: 10.1007/s13402-022-00765-7. View