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Weighted gene co‑expression network analysis of the association between upregulated AMD1, EN1 and VGLL1 and the progression and poor prognosis of breast cancer

  • Authors:
    • Lijie Yang
    • Xuanfei Li
    • Yixing Luo
    • Tiecheng Yang
    • Huaqiao Wang
    • Liwen Shi
    • Maohui Feng
    • Wei Xie
  • View Affiliations / Copyright

    Affiliations: Department of Gastrointestinal Surgery, Clinical Medical Research Center of Peritoneal Cancer of Wuhan, Clinical Cancer Study Center of Hubei Province, Key Laboratory of Tumor Biological Behavior of Hubei, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China, Department of Emergency, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China
    Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 1030
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    Published online on: July 18, 2021
       https://doi.org/10.3892/etm.2021.10462
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Abstract

Breast cancer is the most prevalent malignancy among females, but the molecular mechanisms involved in its pathogenesis and progression have remained to be fully elucidated. The aim of the present study was to identify novel potential therapeutic targets for breast cancer. The dataset GSE76275 was downloaded from the Gene Expression Omnibus database and weighted gene co‑expression network analysis (WGCNA) was performed to identify hub genes. Furthermore, the dataset GSE25055, containing gene expression data and clinical information, was downloaded to validate the expression and survival association of these hub genes. In addition, the datasets GSE25065 and GSE42568 were used to validate the association between hub gene expression levels and clinical features. Immunohistochemistry (IHC), reverse transcription‑quantitative PCR, as well as proliferation, migration, invasion and apoptosis assays, were used to verify gene expression and function. A total of 4,052 genes were selected for WGCNA and 18 modules were established; the red module was identified as the key module, as it had a strong positive correlation with the tumor grade. Survival analyses of hub genes [S‑adenosylmethionine decarboxylase proenzyme (AMD1), homeobox protein engrailed‑1 (EN1) and vestigial‑like protein (VGLL1)] indicated that higher levels of gene expression were associated with poor prognosis of patients with breast cancer. This association was based on survival analysis of GSE25055 using the Kaplan‑Meier plotter tool. Expression validation revealed that the upregulation of hub genes was associated with advanced tumor grade and malignant molecular subtype (basal‑like). IHC results from the Human Protein Atlas also demonstrated that protein expression levels of the hub genes were higher in tumor tissues compared with those in adjacent normal tissues. Furthermore, the expression levels of AMD1, EN1 and VGLL1 were strongly correlated with each other. These results demonstrated that AMD1 is highly expressed in breast cancer tissues and cells and AMD1 knockdown decreased the proliferation and metastatic potential, while increasing apoptosis of breast cancer cells. These results suggested that AMD1, EN1 and VGLL1 are likely to contribute to breast cancer progression and unfavorable prognosis.
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1 

Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA and Jemal A: Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 68:394–424. 2018.PubMed/NCBI View Article : Google Scholar

2 

Marusyk A and Polyak K: Tumor heterogeneity: Causes and consequences. Biochim Biophys Acta. 1805:105–117. 2010.PubMed/NCBI View Article : Google Scholar

3 

Reis-Filho JS and Pusztai L: Gene expression profiling in breast cancer: Classification, prognostication, and prediction. Lancet. 378:1812–1823. 2011.PubMed/NCBI View Article : Google Scholar

4 

Bahnassy A, Mohanad M, Ismail MF, Shaarawy S, El-Bastawisy A and Zekri AR: Molecular biomarkers for prediction of response to treatment and survival in triple negative breast cancer patients from Egypt. Exp Mol Pathol. 99:303–311. 2015.PubMed/NCBI View Article : Google Scholar

5 

Garrido-Castro AC, Lin NU and Polyak K: Insights into molecular classifications of triple-negative breast cancer: Improving patient selection for treatment. Cancer Discov. 9:176–198. 2019.PubMed/NCBI View Article : Google Scholar

6 

Abramson VG, Lehmann BD, Ballinger TJ and Pietenpol JA: Subtyping of triple-negative breast cancer: Implications for therapy. Cancer. 121:8–16. 2015.PubMed/NCBI View Article : Google Scholar

7 

Jhan JR and Andrechek ER: Triple-negative breast cancer and the potential for targeted therapy. Pharmacogenomics. 18:1595–1609. 2017.PubMed/NCBI View Article : Google Scholar

8 

Damaskos C, Garmpi A, Nikolettos K, Vavourakis M, Diamantis E, Patsouras A, Farmaki P, Nonni A, Dimitroulis D, Mantas D, et al: Triple-negative breast cancer: The progress of targeted therapies and future tendencies. Anticancer Res. 39:5285–5296. 2019.PubMed/NCBI View Article : Google Scholar

9 

Langfelder P and Horvath S: WGCNA: An R package for weighted correlation network analysis. BMC Bioinformatics. 9(559)2008.PubMed/NCBI View Article : Google Scholar

10 

Liu H, Sun Y, Tian H, Xiao X, Zhang J, Wang Y and Yu F: Characterization of long non-coding RNA and messenger RNA profiles in laryngeal cancer by weighted gene co-expression network analysis. Aging (Albany NY). 11:10074–10099. 2019.PubMed/NCBI View Article : Google Scholar

11 

Yang J, Li C, Zhou J, Liu X and Wang S: Identification of prognostic genes in leiomyosarcoma by gene co-expression network analysis. Front Genet. 10(1408)2019.PubMed/NCBI View Article : Google Scholar

12 

Wang WJ, Guo CA, Li R, Xu ZP, Yu JP, Ye Y, Zhao J, Wang J, Wang WA, Zhang A, et al: Long non-coding RNA CASC19 is associated with the progression and prognosis of advanced gastric cancer. Aging (Albany NY). 11:5829–5847. 2019.PubMed/NCBI View Article : Google Scholar

13 

Burstein MD, Tsimelzon A, Poage GM, Covington KR, Contreras A, Fuqua SA, Savage MI, Osborne CK, Hilsenbeck SG, Chang JC, et al: Comprehensive genomic analysis identifies novel subtypes and targets of triple-negative breast cancer. Clin Cancer Res. 21:1688–1698. 2015.PubMed/NCBI View Article : Google Scholar

14 

Clarke C, Madden SF, Doolan P, Aherne ST, Joyce H, O'Driscoll L, Gallagher WM, Hennessy BT, Moriarty M, Crown J, et al: Correlating transcriptional networks to breast cancer survival: A large-scale coexpression analysis. Carcinogenesis. 34:2300–2308. 2013.PubMed/NCBI View Article : Google Scholar

15 

Hatzis C, Pusztai L, Valero V, Booser DJ, Esserman L, Lluch A, Vidaurre T, Holmes F, Souchon E, Wang H, et al: A genomic predictor of response and survival following taxane-anthracycline chemotherapy for invasive breast cancer. JAMA. 305:1873–1881. 2011.PubMed/NCBI View Article : Google Scholar

16 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001.PubMed/NCBI View Article : Google Scholar

17 

Kim YJ, Sung M, Oh E, Vrancken MV, Song JY, Jung K and Choi YL: Engrailed 1 overexpression as a potential prognostic marker in quintuple-negative breast cancer. Cancer Biol Ther. 19:335–345. 2018.PubMed/NCBI View Article : Google Scholar

18 

Castilla M, López-García MA, Atienza MR, Rosa-Rosa JM, Díaz-Martín J, Pecero ML, Vieites B, Romero-Pérez L, Benítez J, Calcabrini A and Palacios J: VGLL1 expression is associated with a triple-negative basal-like phenotype in breast cancer. Endocr Relat Cancer. 21:587–599. 2014.PubMed/NCBI View Article : Google Scholar

19 

Lim HK, Rahim AB, Leo VI, Das S, Lim TC, Uemura T, Igarashi K, Common J and Vardy LA: Polyamine regulator AMD1 promotes cell migration in epidermal wound healing. J Invest Dermatol. 138:2653–2665. 2018.PubMed/NCBI View Article : Google Scholar

20 

Zabala-Letona A, Arruabarrena-Aristorena A, Martín-Martín N, Fernandez-Ruiz S, Sutherland JD, Clasquin M, Tomas-Cortazar J, Jimenez J, Torres I, Quang P, et al: mTORC1-dependent AMD1 regulation sustains polyamine metabolism in prostate cancer. Nature. 547:109–113. 2017.PubMed/NCBI View Article : Google Scholar

21 

Stone L: Prostate cancer: Mechanisms of cancer metabolism: mTORC1 mediates AMD1. Nat Rev Urol. 14(454)2017.PubMed/NCBI View Article : Google Scholar

22 

Chen K, Liu H, Liu Z, Luo S, Patz EF Jr, Moorman PG, Su L, Shen S, Christiani DC and Wei Q: Genetic variants in RUNX3, AMD1 and MSRA in the methionine metabolic pathway and survival in nonsmall cell lung cancer patients. Int J Cancer. 145:621–631. 2019.PubMed/NCBI View Article : Google Scholar

23 

Xu L, You X, Cao Q, Huang M, Hong LL, Chen XL, Lei L, Ling ZQ and Chen Y: Polyamine synthesis enzyme AMD1 is closely associated with tumorigenesis and prognosis of human gastric cancers. Carcinogenesis. 41:214–222. 2020.PubMed/NCBI View Article : Google Scholar

24 

Peluffo G, Subedee A, Harper NW, Kingston N, Jovanović B, Flores F, Stevens LE, Beca F, Trinh A, Chilamakuri CS, et al: EN1 is a transcriptional dependency in triple-negative breast cancer associated with brain metastasis. Cancer Res. 79:4173–4183. 2019.PubMed/NCBI View Article : Google Scholar

25 

Bell D, Bell A, Roberts D, Weber RS and El-Naggar AK: Developmental transcription factor EN1-a novel biomarker in human salivary gland adenoid cystic carcinoma. Cancer. 118:1288–1292. 2012.PubMed/NCBI View Article : Google Scholar

26 

Miura K, Akashi T, Ando N, Ayabe S, Kayamori K, Namiki T and Eishi Y: Homeobox transcriptional factor engrailed homeobox 1 is expressed specifically in normal and neoplastic sweat gland cells. Histopathology. 72:1199–1208. 2018.PubMed/NCBI View Article : Google Scholar

27 

Zecca M and Struhl G: A feed-forward circuit linking wingless, fat-dachsous signaling, and the warts-hippo pathway to drosophila wing growth. PLoS Biol. 8(e1000386)2010.PubMed/NCBI View Article : Google Scholar

28 

Mori S, Takeuchi T, Ishii Y and Kukimoto I: The transcriptional cofactor VGLL1 drives transcription of human papillomavirus early genes via TEAD1. J Virol. 94:e01945–e01919. 2020.PubMed/NCBI View Article : Google Scholar

29 

Kim BK, Cheong JH, Im JY, Ban HS, Kim SK, Kang MJ, Lee J, Kim SY, Park KC, Paik S and Won M: PI3K/AKT/β-catenin signaling regulates vestigial-like 1 which predicts poor prognosis and enhances malignant phenotype in gastric cancer. Cancers (Basel). 11(1923)2019.PubMed/NCBI View Article : Google Scholar

30 

Kundishora AJ, Reeves BC, Nelson-Williams C, Hong CS, Gopal PP, Snuderl M, Kahle KT and Erson-Omay EZ: Novel EWSR1-VGLL1 fusion in a pediatric neuroepithelial neoplasm. Clin Genet. 97:791–792. 2020.PubMed/NCBI View Article : Google Scholar

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Copy and paste a formatted citation
Spandidos Publications style
Yang L, Li X, Luo Y, Yang T, Wang H, Shi L, Feng M and Xie W: Weighted gene co‑expression network analysis of the association between upregulated AMD1, EN1 and VGLL1 and the progression and poor prognosis of breast cancer. Exp Ther Med 22: 1030, 2021.
APA
Yang, L., Li, X., Luo, Y., Yang, T., Wang, H., Shi, L. ... Xie, W. (2021). Weighted gene co‑expression network analysis of the association between upregulated AMD1, EN1 and VGLL1 and the progression and poor prognosis of breast cancer. Experimental and Therapeutic Medicine, 22, 1030. https://doi.org/10.3892/etm.2021.10462
MLA
Yang, L., Li, X., Luo, Y., Yang, T., Wang, H., Shi, L., Feng, M., Xie, W."Weighted gene co‑expression network analysis of the association between upregulated AMD1, EN1 and VGLL1 and the progression and poor prognosis of breast cancer". Experimental and Therapeutic Medicine 22.3 (2021): 1030.
Chicago
Yang, L., Li, X., Luo, Y., Yang, T., Wang, H., Shi, L., Feng, M., Xie, W."Weighted gene co‑expression network analysis of the association between upregulated AMD1, EN1 and VGLL1 and the progression and poor prognosis of breast cancer". Experimental and Therapeutic Medicine 22, no. 3 (2021): 1030. https://doi.org/10.3892/etm.2021.10462
Copy and paste a formatted citation
x
Spandidos Publications style
Yang L, Li X, Luo Y, Yang T, Wang H, Shi L, Feng M and Xie W: Weighted gene co‑expression network analysis of the association between upregulated AMD1, EN1 and VGLL1 and the progression and poor prognosis of breast cancer. Exp Ther Med 22: 1030, 2021.
APA
Yang, L., Li, X., Luo, Y., Yang, T., Wang, H., Shi, L. ... Xie, W. (2021). Weighted gene co‑expression network analysis of the association between upregulated AMD1, EN1 and VGLL1 and the progression and poor prognosis of breast cancer. Experimental and Therapeutic Medicine, 22, 1030. https://doi.org/10.3892/etm.2021.10462
MLA
Yang, L., Li, X., Luo, Y., Yang, T., Wang, H., Shi, L., Feng, M., Xie, W."Weighted gene co‑expression network analysis of the association between upregulated AMD1, EN1 and VGLL1 and the progression and poor prognosis of breast cancer". Experimental and Therapeutic Medicine 22.3 (2021): 1030.
Chicago
Yang, L., Li, X., Luo, Y., Yang, T., Wang, H., Shi, L., Feng, M., Xie, W."Weighted gene co‑expression network analysis of the association between upregulated AMD1, EN1 and VGLL1 and the progression and poor prognosis of breast cancer". Experimental and Therapeutic Medicine 22, no. 3 (2021): 1030. https://doi.org/10.3892/etm.2021.10462
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