Abstract
BackgroundUbiquitination is a reversible process of posttranslational protein modification through the action of the family of deubiquitylating enzymes which contain ubiquitin-specific protease 9x (USP9X). Recent evidence indicates that USP9X is involved in the progression of various human cancers. The aim was to detect the expression of USP9X in the progression from normal epithelium to invasive esophageal squamous cell cancer (ESCC) and evaluate the relevance of USP9X expression to the tumor progression and prognosis.MethodsIn this study, USP9X immunohistochemical analysis was performed on tissues constructed from ESCC combined with either normal epithelium or adjacent precursor tissues of 102 patients. All analyses were performed by SPSS 13.0 software.ResultsWe observed that the level of high USP9X expression increased gradually in the transformation from normal epithelium (4.0%), to low grade intraepithelial neoplasia (10.5%), then to high grade intraepithelial neoplasia (28.6%), and finally to invasive ESCC (40.2%). The expression of USP9X was found to be significantly different between the normal mucosa and ESCC (P < 0.001), and between low grade intraepithelial neoplasia and high grade intraepithelial neoplasia (p = 0.012). However, no difference was observed between the high expression of USP9X in normal mucosa and low grade intraepithelial neoplasia (P = 0.369), nor between high grade intraepithelial neoplasia and ESCC (p = 0.115). Interestingly, the most intensive staining for USP9X was usually observed in the basal and lower spinous layers of the esophageal epithelium with precursor lesions which often resulted in the earliest malignant lesion. USP9X expression status was positively associated with both depth of invasion (p = 0.046) and lymph node metastasis (p = 0.032). Increased USP9X expression was significantly correlated to poorer survival rate in ESCC patients (p = 0.001). When adjusted by multivariate analysis, USP9X expression (HR 2.066, P = 0.005), together with TNM stage (HR 1.702, P = 0.042) was an independent predictor for overall survival.ConclusionsUp-regulation of USP9X plays an important role in formation and progression of precancerous lesions in ESCC and USP9X expression levels were significantly correlated with the survival of ESCC patients. Thus, USP9X could be considered as a potential biomarker and prognostic predictor for ESCC.Virtual slidesThe virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1945302932102737
Highlights
Ubiquitination is a reversible process of posttranslational protein modification through the action of the family of deubiquitylating enzymes which contain ubiquitin-specific protease 9x (USP9X)
In the same study, increased USP9X in multiple myeloma patients correlates with poor survival and the authors conclude that USP9X stabilizes MCL1, one member of pro-survival BCL2 family, and promotes tumor cell survival [15]
Of the remaining 77 cases, there were 20 cases of esophageal squamous cell cancer (ESCC) combined with low grade intraepithelial neoplasia, cases were ESCC combined with high grade intraepithelial neoplasia, and cases were ESCC combined with both precursor lesions
Summary
Ubiquitination is a reversible process of posttranslational protein modification through the action of the family of deubiquitylating enzymes which contain ubiquitin-specific protease 9x (USP9X). The aim was to detect the expression of USP9X in the progression from normal epithelium to invasive esophageal squamous cell cancer (ESCC) and evaluate the relevance of USP9X expression to the tumor progression and prognosis. Ubiquitination has been found to be a key regulatory mechanism in multiple biological processes and controls almost all aspects of protein function through the reversible posttranslational modification of cellular proteins by the action of ubiquitylating and deubiquitylating enzymes (DUBs) [5,9]. In the same study, increased USP9X in multiple myeloma patients correlates with poor survival and the authors conclude that USP9X stabilizes MCL1, one member of pro-survival BCL2 family, and promotes tumor cell survival [15]. WP1130 has been found to promote Mcl degradation and increases tumor cell sensitivity to chemotherapies in colon adenocarcinomas and lung cancers [17]
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