Abstract
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. The aim of this study was to investigate the role of USP22 and its association with potential targets in patients with NB. The potential clinicopathological significance of USP22 expression in NB was studied using immunohistochemistry, immunohistochemical staining assessment and statistical analyses. 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). 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.
Highlights
Neuroblastoma (NB) is a rare type of cancer that develops in children and infants at an annual incidence rate of between 6 and 10 per million.[1]
Our results indicate a significant association between Ubiquitin-specific protease 22 (USP22) level and poor prognosis in NB
Ubiquitin-specific protease 22 is associated with poor prognosis in neuroblastoma
Summary
Neuroblastoma (NB) is a rare type of cancer that develops in children and infants at an annual incidence rate of between 6 and 10 per million.[1]. Ubiquitin-specific protease 22 (USP22) is an element of the 11-Polycomb/cancer stem cell signature that is involved in the alteration of histone ubiquitination, which makes it a valuable marker for predicting the therapeutic response of individual patients with cancer.4 Elevated USP22 expression is related to a poor prognosis in colo rectal, gastric, liver, lung, and breast cancers.[5–9]. The USP22 is the essential protein linked to the DUB module It modifies histones H2A and H2B, which facilitate a variety of cellular events, including gene regulation. USP22 modulates growth and oncogenic transformation by regulating transcription factors, such as BMI-1, c-MYC, p53, TRF1, and SIRT1.11–16 These findings provide evidence that USP22 is vital in tumor progression and advancement; it is a valuable target as an NB marker. 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
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