Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
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ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
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Advances in Clinical and Experimental Medicine

2020, vol. 29, nr 3, March, p. 295–300

doi: 10.17219/acem/115089

Publication type: original article

Language: English

License: Creative Commons Attribution 3.0 Unported (CC BY 3.0)

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Ubiquitin-specific protease 22 is associated with poor prognosis in neuroblastoma

Qu Zhibo1,2,A,B,C,D, Liu Lianxin1,A,F

1 Department of Heptic Surgery, First Affiliated Hospital of Harbin Medical University, China

2 Department of General Surgery, Harbin Children’s Hospital, China


Background. Ubiquitin-specific protease 22 (USP22) alters histone ubiquitination and is considered to be an oncogenic factor involved in tumor progression. The USP22 aberrance has been implicated in several malignancies, but whether USP22 plays a role in neuroblastoma (NB) remains unclear. To the best of our knowledge, the clinicopathological significance of USP22 expression in NB has not been previously reported in the English-language medical literature.
Objectives. The aim of this study was to investigate the role of USP22 and its association with potential targets in patients with NB.
Material and Methods. The potential clinicopathological significance of USP22 expression in NB was studied using immunohistochemistry, immunohistochemical staining assessment and statistical analyses.
Results. Based on the immunohistochemical analysis, the USP22 protein was detected more manifestly in NB tissues than in healthy peritumoral tissue. Furthermore, an association between USP22, lymph node metastasis and NB clinical stage was observed, whereby the level of USP22 protein was higher in stage III–IV specimens than in stage I–II specimens (p < 0.05). Furthermore, tumors expressing USP22 were associated with poorer patient prognosis than the USP22-negative tumors. The multivariate Cox regression analysis suggested that the level of USP22 protein is a predictive factor for survival (p < 0.05).
Conclusion. Our results indicate a significant association between USP22 level and poor prognosis in NB. Thus, USP22 represents a valuable biomarker for predicting the outcome of patients with NB.

Key words

neuroblastoma, ubiquitin-specific protease 22, poor prognostic

References (24)

  1. Kiyonari S, Kadomatsu K. Neuroblastoma models for insights into tumorigenesis and new therapies. Expert Opin Drug Discov. 2015;10(1):53–62.
  2. Yang S, Zheng J, Xiao X, et al. SOX2 promotes tumorigenicity and inhibits the differentiation of I-type neuroblastoma cells. Int J Oncol. 2014;46(1):317–323.
  3. Bansal D, Totadri S, Chinnaswamy G, et al. Management of neuroblastoma: ICMR Consensus Document. Indian J Pediatr. 2017;84(6):446–455.
  4. Glinsky GV. Death-from-cancer signatures and stem cell contribution to metastatic cancer. Cell Cycle. 2005;4(9):1171–1175.
  5. Liu YL, Yang YM, Xu H, Dong XS. Increased expression of ubiquitin-specific protease 22 can promote cancer progression and predict therapy failure in human colorectal cancer. J Gastroenterol Hepatol. 2010;25(11):1800–1805.
  6. He Y, Jin YJ, Zhang YH, et al. Ubiquitin-specific peptidase 22 overexpression may promote cancer progression and poor prognosis in human gastric carcinoma. Transl Res. 2015;165(3):407–416.
  7. Tang B, Liang X, Tang F, et al. Expression of USP22 and Survivin is an indicator of malignant behavior in hepatocellular carcinoma. Int J Oncol. 2015;47(6):2208–2216.
  8. Hu J, Yang D, Zhang H, et al. USP22 promotes tumor progression and induces epithelial-mesenchymal transition in lung adenocarcinoma. Lung Cancer. 2015;88(3):239–245.
  9. Zhang Y, Yao L, Zhang X, et al. Elevated expression of USP22 in correlation with poor prognosis in patients with invasive breast cancer. J Cancer Res Clin Oncol. 2011;137(8):1245–1253.
  10. Melo-Cardenas J, Zhang Y, Zhang DD, Fang D. Ubiquitin-specific peptidase 22 functions and its involvement in disease. Oncotarget. 2016;7(28):44848–44856.
  11. Ma Y, Fu HL, Wang Z, et al. USP22 maintains gastric cancer stem cell stemness and promotes gastric cancer progression by stabilizing BMI1 protein. Oncotarget. 2017;8(20):33329–33342.
  12. Vijayalingam S, Subramanian T, Zhao LJ, Chinnadurai G. The cellular protein complex associated with a transforming region of E1A contains c-MYC. J Virol. 2015;90(2):1070–1079.
  13. Zhou D, Liu P, Sun DW, et al. USP22 down-regulation facilitates human retinoblastoma cell aging and apoptosis via inhibiting TERT/P53 pathway. Eur Rev Med Pharmacol Sci. 2017;21(12):2785–2792.
  14. Ling S, Li J, Shan Q, et al. USP22 mediates the multidrug resistance of hepatocellular carcinoma via the SIRT1/AKT/MRP1 signaling pathway. Mol Oncol. 2017;11(6):682–695.
  15. Zhang XY, Pfeiffer HK, Thorne AW, McMahon SB. USP22, an hSAGA subunit and potential cancer stem cell marker, reverses the polycomb-catalyzed ubiquitylation of histone H2A. Cell Cycle. 2008;7(11):1522–1524.
  16. Piao S, Liu Y, Hu J, et al. USP22 is useful as a novel molecular marker for predicting disease progression and patient prognosis of oral squamous cell carcinoma. PLoS One. 2012;7(8):e42540.
  17. Maris JM. Recent advances in neuroblastoma. N Engl J Med. 2010;362(23):2202–2211.
  18. Liu YL, Yang YM, Xu H, Dong XS. Aberrant expression of USP22 is associated with liver metastasis and poor prognosis of colorectal cancer. J Surg Oncol. 2011;103(3):283–289.
  19. Xiong J, Che X, Li X, Yu H, Gong Z, Li W. Cloning and characterization of the human USP22 gene promoter. PLoS One. 2012;7(12):e52716.
  20. Wang L, Dent SY. Functions of SAGA in development and disease. Epigenomics. 2014;6(3):329–339.
  21. Liu YL, Zheng J, Tang LJ, et al. The deubiquitinating enzyme activity of USP22 is necessary for regulating HeLa cell growth. Gene. 2015;572(1):49–56.
  22. Atanassov BS, Dent SY. USP22 regulates cell proliferation by deubiquitinating the transcriptional regulator FBP1. EMBO Rep. 2011;2(9):924–930.
  23. Li Y, Yang Y, Li J, et al. USP22 drives colorectal cancer invasion and metastasis via epithelial–mesenchymal transition by activating AP4. Oncotarget. 2017;8(20):32683–32695.
  24. Yang H, Liu S, He WT, Zhao J, Jiang LL, Hu HY. Aggregation of polyglutamine-expanded ataxin 7 protein specifically sequesters ubiquitin-specific protease 22 and deteriorates its deubiquitinating function in the Spt-Ada-Gcn5-acetyltransferase (SAGA) complex. J Biol Chem. 2015;290(36):21996–22004.