Comprehensive Analysis of the Expression and Prognostic Significance of the CENP Family in Breast Cancer

Overview

Journal Int J Gen Med

Publisher Dove Medical Press

Specialty General Medicine

Date 2022 Apr 5

PMID 35378917

Authors

Xueliang Liu

Yunjiang Liu

Affiliations

Soon will be listed here.

Abstract

Background: Centromere proteins (CENPs) are a set of protein-coding genes involved in the transient assembly of the kinetochore which occurs during mitosis. This study intended to clarify the expression patterns, prognosis and potential mechanisms of CENPs in breast cancer (BC).

Methods: Coexpedia was used to screen GEO datasets and PubMed articles related to CENPs and BC. CENPs expressions, prognosis and alteration were analyzed by Oncomine, Ualcan and Kaplan Meier plotter and cBioPortal. The correlation and interaction of CENPs was performed by Breast Cancer Gene-Expression Miner, GeneMANIA and STRING portal. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were conducted to clarify the functional roles of CENPs. CENPF, E, U, A, N, I, K, W, M, L were selected for further analysis.

Results: All CENPs were highly expressed in BC compared to normal tissue. High expression of CENPF, E, U, A, N, I, W, M, L and CENPF, E, U, A, N, I, M correlated with worse relapse free survival (RFS) and worse overall survival (OS), respectively. All of 10 CENPs indicated positive correlations and complex interactions between each other at mRNA expression and protein level. CENPs were enriched GO terms mainly in centromere complex assembly and KEGG terms in progesterone-mediated oocyte maturation, cell cycle and oocyte meiosis.

Conclusion: The 10 CENPs could be diagnostic biomarkers and all of them except CENPK can be used as prognosis biomarkers in BC. CENPs play an oncogenic role and may be the potential therapy targets of treatment for BC patients.

Citing Articles

KHSRP has oncogenic functions and regulates the expression and alternative splicing of DNA repair genes in breast cancer MDA-MB-231 cells.

Paizula X, Wulaying A, Chen D, Ou J Sci Rep. 2024; 14(1):14694.

PMID: 38926398 PMC: 11208542. DOI: 10.1038/s41598-024-64687-0.

Isoform switching leads to downregulation of cytokine producing genes in estrogen receptor positive breast cancer.

Khan M, Hanif W, Alsakhen N, Jabbar B, Shamkh I, Alsaiari A Front Genet. 2023; 14:1230998.

PMID: 37900178 PMC: 10611502. DOI: 10.3389/fgene.2023.1230998.

Expression profiling of luminal B breast tumor in Indian women.

Ulaganathan K, Puranam K, Mukta S, Hanumanth S J Cancer Res Clin Oncol. 2023; 149(15):13645-13664.

PMID: 37516983 DOI: 10.1007/s00432-023-05195-y.

References

Shahid M, Kim M, Lee M, Yeon A, You S, Kim H . Downregulation of CENPF Remodels Prostate Cancer Cells and Alters Cellular Metabolism. Proteomics. 2019; 19(11):e1900038. PMC: 6633900. DOI: 10.1002/pmic.201900038. View

Hao X, Qu T . Expression of CENPE and its Prognostic Role in Non-small Cell Lung Cancer. Open Med (Wars). 2019; 14:497-502. PMC: 6592151. DOI: 10.1515/med-2019-0053. View

Clarke L, Carbon J . Isolation of a yeast centromere and construction of functional small circular chromosomes. Nature. 1980; 287(5782):504-9. DOI: 10.1038/287504a0. View

Zhou Z, Zhou Z, Huang Z, He S, Chen S . Histone-fold centromere protein W (CENP-W) is associated with the biological behavior of hepatocellular carcinoma cells. Bioengineered. 2020; 11(1):729-742. PMC: 8291794. DOI: 10.1080/21655979.2020.1787776. View

Szklarczyk D, Gable A, Lyon D, Junge A, Wyder S, Huerta-Cepas J . STRING v11: protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets. Nucleic Acids Res. 2018; 47(D1):D607-D613. PMC: 6323986. DOI: 10.1093/nar/gky1131. View

Andres S, Bickett K, Alatoum M, Kalbfleisch T, Brock G, Wittliff J . Interaction between smoking history and gene expression levels impacts survival of breast cancer patients. Breast Cancer Res Treat. 2015; 152(3):545-56. DOI: 10.1007/s10549-015-3507-z. View

Pan T, Zhou D, Shi Z, Qiu Y, Zhou G, Liu J . Centromere protein U (CENPU) enhances angiogenesis in triple-negative breast cancer by inhibiting ubiquitin-proteasomal degradation of COX-2. Cancer Lett. 2019; 482:102-111. DOI: 10.1016/j.canlet.2019.11.003. View

Komatsu M, Yoshimaru T, Matsuo T, Kiyotani K, Miyoshi Y, Tanahashi T . Molecular features of triple negative breast cancer cells by genome-wide gene expression profiling analysis. Int J Oncol. 2012; 42(2):478-506. DOI: 10.3892/ijo.2012.1744. View

Hori T, Amano M, Suzuki A, Backer C, Welburn J, Dong Y . CCAN makes multiple contacts with centromeric DNA to provide distinct pathways to the outer kinetochore. Cell. 2008; 135(6):1039-52. DOI: 10.1016/j.cell.2008.10.019. View

10.

Brown H, Ottewell P, Coleman R, Holen I . The kinetochore protein Cenp-F is a potential novel target for zoledronic acid in breast cancer cells. J Cell Mol Med. 2009; 15(3):501-13. PMC: 3922372. DOI: 10.1111/j.1582-4934.2009.00995.x. View

11.

Park C, Park J, Kim T, Kang Y, Soung N, Zhou M . Mammalian Polo-like kinase 1 (Plk1) promotes proper chromosome segregation by phosphorylating and delocalizing the PBIP1·CENP-Q complex from kinetochores. J Biol Chem. 2015; 290(13):8569-81. PMC: 4375506. DOI: 10.1074/jbc.M114.623546. View

12.

Capra V, Severino M, Rossi A, Nozza P, Doneda C, Perri K . Pituitary deficiency and congenital infiltrating lipomatosis of the face in a girl with deletion of chromosome 1q24.3q31.1. Am J Med Genet A. 2013; 164A(2):495-9. DOI: 10.1002/ajmg.a.36283. View

13.

Li H, Zhang H, Wang Y . Centromere protein U facilitates metastasis of ovarian cancer cells by targeting high mobility group box 2 expression. Am J Cancer Res. 2018; 8(5):835-851. PMC: 5992511. View

14.

Musacchio A, Desai A . A Molecular View of Kinetochore Assembly and Function. Biology (Basel). 2017; 6(1). PMC: 5371998. DOI: 10.3390/biology6010005. View

15.

Montojo J, Zuberi K, Rodriguez H, Kazi F, Wright G, Donaldson S . GeneMANIA Cytoscape plugin: fast gene function predictions on the desktop. Bioinformatics. 2010; 26(22):2927-8. PMC: 2971582. DOI: 10.1093/bioinformatics/btq562. View

16.

Nagini S . Breast Cancer: Current Molecular Therapeutic Targets and New Players. Anticancer Agents Med Chem. 2016; 17(2):152-163. DOI: 10.2174/1871520616666160502122724. View

17.

Yu G, Wang L, Han Y, He Q . clusterProfiler: an R package for comparing biological themes among gene clusters. OMICS. 2012; 16(5):284-7. PMC: 3339379. DOI: 10.1089/omi.2011.0118. View

18.

Sun J, Huang J, Lan J, Zhou K, Gao Y, Song Z . Overexpression of CENPF correlates with poor prognosis and tumor bone metastasis in breast cancer. Cancer Cell Int. 2019; 19:264. PMC: 6788011. DOI: 10.1186/s12935-019-0986-8. View

19.

Kagawa N, Hori T, Hoki Y, Hosoya O, Tsutsui K, Saga Y . The CENP-O complex requirement varies among different cell types. Chromosome Res. 2014; 22(3):293-303. PMC: 4129241. DOI: 10.1007/s10577-014-9404-1. View

20.

Fritzler M, Rattner J, Luft L, Edworthy S, Casiano C, Peebles C . Historical perspectives on the discovery and elucidation of autoantibodies to centromere proteins (CENP) and the emerging importance of antibodies to CENP-F. Autoimmun Rev. 2010; 10(4):194-200. DOI: 10.1016/j.autrev.2010.09.025. View