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Programmed cell death 10 can be used as a potential biomarker for ankylosing spondylitis diagnosis and treatment

Spinal Cord volume 62, pages 99–103 (2024)Cite this article

Subjects

Abstract

Study design

Diagnostic study.

Objective

Programmed cell death 10 (PDCD10) is a new versatile molecule involved in signal transduction regulation in angiogenesis and tumors. The potential of using it as a biomarker for the diagnosis of ankylosing spondylitis (AS) is still unknown.

Setting

University laboratory in Gannan Medical University, China.

Methods

Expression of PDCD10 was analyzed using clinical samples of patients with AS and Gene Expression Omnibus (GEO) data GDS5231. To explore its function, PDCD10 was upregulated and downregulated in synovial cells. Spearman analysis was used to study the association between PDCD10 and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS). The Receiver operating characteristic (ROC) curve was applied to evaluate the sensitivity and specificity of PDCD10.

Results

Expression of PDCD10 was upregulated in patients with AS and it is capable of promoting the calcification of synovial cells. A positive association between PDCD10 and the BASDAI and the mSASSS was observed. The area under the ROC curve (AUC) of PDCD10 was 82% with a 95% confidence interval of [0.772, 0.868].

Conclusions

PDCD10 is upregulated in patients with AS and it can promote the calcification of synovial cells in vitro. PDCD10 is positively associated with outcome parameters of AS. ROC analysis of PDCD10 suggests that it can be used as a biomarker for the diagnosis and treatment of AS.

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Fig. 1: Expression of PDCD10.
Fig. 2: Functional studies of PDCD10.
Fig. 3: Spearman analysis of PDCD10 and AS evaluation indexes.
Fig. 4: ROC of PDCD10.

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Data availability

GDS5231 can be obtained from the NCBI network: https://www.ncbi.nlm.nih.gov/geoprofiles. Others are available on request.

References

  1. Ebrahimiadib N, Berijani S, Ghahari M, Pahlaviani FG. Ankylosing spondylitis. J Ophthalmic Vis Res. 2021;16:462–9.

    PubMed  PubMed Central  Google Scholar 

  2. Braun J, Sieper J. Ankylosing spondylitis. Lancet. 2007;369:1379–90.

    Article  PubMed  Google Scholar 

  3. Sparks JA, Costenbader KH. Genetics, environment, and gene-environment interactions in the development of systemic rheumatic diseases. Rheum Dis Clin North Am. 2014;40:637–57.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Wang XB, Ellis JJ, Pennisi DJ, Song X, Batra J, Hollis K, et al. Transcriptome analysis of ankylosing spondylitis patients before and after TNF-alpha inhibitor therapy reveals the pathways affected. Genes Immun. 2017;18:184–90.

    Article  CAS  PubMed  Google Scholar 

  5. Poddubnyy D, Sieper J. Diagnostic delay in axial spondyloarthritis - a past or current problem? Curr Opin Rheumatol. 2021;33:307–12.

    Article  PubMed  Google Scholar 

  6. Sieper J, Poddubnyy D. New evidence on the management of spondyloarthritis. Nat Rev Rheumatol. 2016;12:282–95.

    Article  CAS  PubMed  Google Scholar 

  7. Bergametti F, Denier C, Labauge P, Arnoult M, Boetto S, Clanet M, et al. Mutations within the programmed cell death 10 gene cause cerebral cavernous malformations. Am J Hum Genet. 2005;76:42–51.

    Article  CAS  PubMed  Google Scholar 

  8. Valentino M, Dejana E, Malinverno M. The multifaceted PDCD10/CCM3 gene. Genes Dis. 2021;8:798–813.

    Article  CAS  PubMed  Google Scholar 

  9. Ørnbjerg LM, Brahe CH, Askling J, Ciurea A, Mann H, Onen F, et al. Treatment response and drug retention rates in 24 195 biologic-naive patients with axial spondyloarthritis initiating TNFi treatment: routine care data from 12 registries in the EuroSpA collaboration. Ann Rheum Dis. 2019;78:1536–44.

    Article  PubMed  Google Scholar 

  10. Wordsworth BP, Cohen CJ, Davidson C, Vecellio M. Perspectives on the genetic associations of ankylosing spondylitis. Front Immunol. 2021;12:603726.

  11. Chen B, Li J, He C, Li D, Tong W, Zou Y, et al. Role of HLA-B27 in the pathogenesis of ankylosing spondylitis. Mol Med Rep. 2017;15:1943–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Pimentel-Santos FM, Mourão AF, Ribeiro C, Costa J, Santos H, Barcelos A, et al. Spectrum of ankylosing spondylitis in Portugal. Development of BASDAI, BASFI, BASMI and mSASSS reference centile charts. Clin Rheumatol. 2012;31:447–54.

    Article  PubMed  Google Scholar 

  13. Khanna M, Keightley A. MRI of the axial skeleton manifestations of ankylosing spondylitis. Clin Radiol. 2005;60:135–6.

    Article  CAS  PubMed  Google Scholar 

  14. Rudwaleit M, Khan MA, Sieper J. The challenge of diagnosis and classification in early ankylosing spondylitis: do we need new criteria? Arthritis Rheum. 2010;52:1000–8.

    Article  Google Scholar 

  15. Creemers MC, Franssen MJ, van’t Hof MA, Gribnau FW, van de Putte LB, van Riel PL. Assessment of outcome in ankylosing spondylitis: an extended radiographic scoring system. Ann Rheum Dis. 2005;64:127–9.

    Article  CAS  PubMed  Google Scholar 

  16. Wang Y, Liu H, Zhang Y, Ma D. cDNA cloning and expression of an apoptosis-related gene, humanTFAR15 gene. Sci China C Life Sci. 1999;42:323–9.

    Article  CAS  PubMed  Google Scholar 

  17. Stahl S, Gaetzner S, Voss K, Brackertz B, Schleider E, Sürücü O, et al. Novel CCM1, CCM2, and CCM3 mutations in patients with cerebral cavernous malformations: in-frame deletion in CCM2 prevents formation of a CCM1/CCM2/CCM3 protein complex. Hum Mutat. 2008;29:709–17.

    Article  CAS  PubMed  Google Scholar 

  18. Cigoli MS, Avemaria F, De Benedetti S, Gesu GP, Accorsi LG, Parmigiani S, et al. PDCD10 gene mutations in multiple cerebral cavernous malformations. PLoS ONE. 2014;9:e110438.

    Article  ADS  PubMed  PubMed Central  Google Scholar 

  19. Huang DN, Zhao HS. PDCD10,a novel signal transduction regulating molecule with multiple functions. Chin J Biochem Mol Biol. 2013;24:306–10.

    Google Scholar 

  20. Ma X, Zhao H, Shan J, Long F, Chen Y, Chen Y, et al. PDCD10 interacts with Ste20-related kinase MST4 to promote cell growth and transformation via modulation of the ERK pathway. Mol Biol Cell. 2007;18:1965–78.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Zhang H, Ma X, Deng X, Chen Y, Mo X, Zhang Y, et al. PDCD10 interacts with STK25 to accelerate cell apoptosis under oxidative stress. Front Biosci. 2012;17:2295–305.

    Article  Google Scholar 

  22. Ranganathan V, Gracey E, Brown MA, Inman RD, Haroon N. Pathogenesis of ankylosing spondylitis - recent advances and future directions. Nat Rev Rheumatol. 2017;13:359–67.

    Article  CAS  PubMed  Google Scholar 

  23. Brown MA, Kenna T, Wordsworth BP. Genetics of ankylosing spondylitis–insights into pathogenesis. Nat Rev Rheumatol. 2016;12:81–91.

    Article  CAS  PubMed  Google Scholar 

  24. Danve A, O’Dell J. The ongoing quest for biomarkers in ankylosing spondylitis. Int J Rheum Dis. 2015;18:826–34.

    Article  CAS  PubMed  Google Scholar 

  25. Corr M. Wnt signaling in ankylosing spondylitis. Clin Rheumatol. 2014;33:759–62.

    Article  PubMed  Google Scholar 

  26. Yang PT, Xiao WG, Qin L, Zhao LJ, He LM, Ito M. A pilot study on changes of macrophage colony stimulating factor and transforming growth factor beta1 in male patients with ankylosing spondylitis taking thalidomide. Ann Rheum Dis. 2010;69:781–2.

    Article  CAS  PubMed  Google Scholar 

  27. Zhang H, Lin M, Dong C, Tang Y, An L, Ju J, et al. An MST4-pbeta-Catenin(Thr40) signaling axis controls intestinal stem cell and tumorigenesis. Adv Sci. 2021;8:e2004850.

    Article  Google Scholar 

  28. Thompson BJ, Sahai E. MST kinases in development and disease. J Cell Biol. 2015;210:871–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

All the authors would thank anonymous reviewers and the editor for improving our manuscript. This work was supported by the Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular of Ministry of Education of Gannan Medical University (XN202013), Science and Technology Research Project of Jiangxi Provincial Department of Education (GJJ201528), Startup Foundation for Advanced Talents of Gannan Medical University (QD202124).

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Authors and Affiliations

  1. Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular of Ministry of Education, Gannan Medical University, Ganzhou, 341000, Jiangxi, People’s Republic of China

    Wen-Juan Ni & Xiao-Min Leng

  2. School of Basic Medicine, Gannan Medical University, Ganzhou, 341000, Jiangxi, People’s Republic of China

    Wen-Juan Ni & Xiao-Min Leng

  3. The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, 453100, Henan, People’s Republic of China

    Xiao-Min Leng

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  1. Wen-Juan Ni
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Contributions

Conceptualization and Data curation, WJN and XML; Funding acquisition, WJN and XML; Methodology, WJN; Project administration, XML; Supervision, XML; Writing-original draft, WJN; Writing-review & editing, WJN and XML.

Corresponding author

Correspondence to Xiao-Min Leng.

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The authors declare no competing interests.

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Ethical approval was obtained from the Ethics Committee of Gannan Medical University (No. 2021241).

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Ni, WJ., Leng, XM. Programmed cell death 10 can be used as a potential biomarker for ankylosing spondylitis diagnosis and treatment. Spinal Cord 62, 99–103 (2024). https://doi.org/10.1038/s41393-023-00952-9

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