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Identification of SMC2 and SMC4 as prognostic markers in breast cancer through bioinformatics analysis

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Abstract

Background

Breast cancer (BRCA) is one of the most common malignant tumors. The structural maintenance of chromosome (SMC) gene family has been shown to play an important role in human cancers. However, the role of SMC families in BRCA is unclear. This study aimed to explore the role and potential clinical value of whole SMCs in BRCA.

Methods

TIMER and UALCAN database were used to analysis the expression level. Genetic variations were analyzed by cBioPortal. Promoter methylation and protein level were analyzed by UCLCAN. GO and KEGG were analyzed by Metascape database. Prognostic value of SMCs was analyzed by Kaplan–Meier and multivariate cox regression analyses. Immune infiltration analysis was conducted by CIBERSORT. Immunotherapy outcome prediction was conducted by Cancer Immunome Atlas. Targeted drug therapy outcome prediction was taken by GDSC and R language. The cell viability was tested by CCK8 and migration was tested by wound healing assay. Xenograft model was used to investigate the in vivo role of SMC2.

Results

Expression levels of SMC1A, SMC2, SMC4, SMC5 and SMC6 mRNA were increased in BRCA tissues, and negatively correlated with promoter methylation. Overexpression of SMC2 and SMC4 was negatively correlated with survival. Function of SMCs family regulatory genes was mainly related to ATPase activity. Expression of most SMCs was negatively correlated with immunotherapy and drug therapy outcomes. Interfere SMC2 and SMC4 decreased IC50 values of 5-fluorouracil and oxaliplatin and inhibited the migration of MCF7 cells. Tumor growth and weights were significantly decreased in si-SMC2 groups.

Conclusions

Combined bioinformatics and clinical specimen analysis verified SMC2 and SMC4 as independent prognostic factors in BRCA, suggesting their significance for the diagnosis and treatment of BRCA.

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Availability of data and materials

The data comes from TCGA (https://portal.gdc.cancer.gov/) public database.

References

  1. Wormann B. Breast cancer: basics, screening, diagnostics and treatment. Med Monatsschr Pharm. 2017;40(2):55–64.

    PubMed  Google Scholar 

  2. Cejuela M, Vethencourt A, Pernas S. Immune checkpoint inhibitors and novel immunotherapy approaches for breast cancer. Curr Oncol Rep. 2022;24(12):1801–19.

    Article  CAS  PubMed  Google Scholar 

  3. Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, Jemal A, Yu XQ, He J. Cancer statistics in China, 2015. CA Cancer J Clin. 2016;66(2):115–32.

    Article  PubMed  Google Scholar 

  4. Zheng RS, Zhang SW, Sun KX, Chen R, Wang SM, Li L, Zeng HM, Wei WW, He J. Cancer statistics in China, 2016. Zhonghua Zhong Liu Za Zhi. 2023;45(3):212–20.

    CAS  PubMed  Google Scholar 

  5. Gonzalez-Angulo AM, Morales-Vasquez F, Hortobagyi GN. Overview of resistance to systemic therapy in patients with breast cancer. Adv Exp Med Biol. 2007;608:1–22.

    Article  CAS  PubMed  Google Scholar 

  6. Losada A, Hirano T. Dynamic molecular linkers of the genome: the first decade of SMC proteins. Genes Dev. 2005;19(11):1269–87.

    Article  CAS  PubMed  Google Scholar 

  7. Nishiwaki T, Daigo Y, Kawasoe T, Nagasawa Y, Ishiguro H, Fujita M, Furukawa Y, Nakamura Y. Isolation and characterization of a human cDNA homologous to the Xenopus laevis XCAP-C gene belonging to the structural maintenance of chromosomes (SMC) family. J Hum Genet. 1999;44(3):197–202.

    Article  CAS  PubMed  Google Scholar 

  8. Li J, He J, Wang Y, Shu Y, Zhou J. SMC1 promotes proliferation and inhibits apoptosis through the NF-κB signaling pathway in colorectal cancer. Oncol Rep. 2019;42(4):1329–42.

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Vincent A, Herman J, Schulick R, Hruban RH, Goggins M. Pancreatic cancer. Lancet. 2011;378(9791):607–20.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Dávalos V, Súarez-López L, Castaño J, Messent A, Abasolo I, Fernandez Y, Guerra-Moreno A, Espín E, Armengol M, Musulen E, et al. Human SMC2 protein, a core subunit of human condensin complex, is a novel transcriptional target of the WNT signaling pathway and a new therapeutic target. J Biol Chem. 2012;287(52):43472–81.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Zhou B, Chen H, Wei D, Kuang Y, Zhao X, Li G, Xie J, Chen P. A novel miR-219-SMC4-JAK2/Stat3 regulatory pathway in human hepatocellular carcinoma. J Exp Clin Cancer Res. 2014;33(1):55.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Jiang L, Zhou J, Zhong D, Zhou Y, Zhang W, Wu W, Zhao Z, Wang W, Xu W, He L, et al. Overexpression of SMC4 activates TGFbeta/Smad signaling and promotes aggressive phenotype in glioma cells. Oncogenesis. 2017;6(3): e301.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Ma RM, Yang F, Huang DP, Zheng M, Wang YL. The prognostic value of the expression of SMC4 mRNA in breast cancer. Dis Markers. 2019;2019:2183057.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Emens LA. Breast cancer immunotherapy: facts and hopes. Clin Cancer Res. 2018;24(3):511–20.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We thank all our colleagues in the laboratory for their assistance during the progression of this study. We acknowledge all the public database used in this study for providing their platforms and contributors for uploading their meaningful datasets.

Funding

This study was supported by grants from the National Natural Science Foundation of China [81703557], Science and Technology Development Fund of Nanjing Medical University (KDNMUB202201), Research and Development Fund of Kangda College of Nanjing Medical University (KD2022KYJJYB013), Kangda College of Nanjing Medical University "Scientific Research Talent Training Program"(KD2021KYRC019), and Innovation and Entrepreneurship Training Program for College Students in Jiangsu Province (KD2023SJCXCY21, KD2023SJCXCY22).

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Author notes

  1. Lili Pei and Yu Li contributed equally to this paper.

Authors and Affiliations

  1. Department of Basic Medical Science, Kangda College of Nanjing Medical University, Lianyungang, 222000, China

    Lili Pei, Wenhao Wu & Siyi Fan

  2. Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, Jiangsu Key Laboratory of Marine Biological Resources and Environment, Co-Innovation Center of Jiangsu Marine Bio-Industry Technology, School of Pharmacy, Jiangsu Ocean University, Lianyungang, 222005, China

    Yu Li, Hao Gu, Siqi Wang, Xiao Shi & Xinxin Si

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  1. Lili Pei
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Contributions

Lili Pei, WenhaoWu, and Siyi Fan: Collected data, conducted the data summary and statistical analysis. Yu Li and Hao Gu: performed experiments and searched for references and helped to write and revise the paper. Xiao Shi: Conducted data analysis and interpretation and wrote the manuscript. Xinxin Si: Assembled data and reviewed the manuscript. All authors contributed to the article and approved the submitted version.

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Correspondence to Xiao Shi or Xinxin Si.

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Pei, L., Li, Y., Gu, H. et al. Identification of SMC2 and SMC4 as prognostic markers in breast cancer through bioinformatics analysis. Clin Transl Oncol (2024). https://doi.org/10.1007/s12094-024-03521-5

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  • DOI: https://doi.org/10.1007/s12094-024-03521-5

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