title: OTUB1 promotes tumor invasion and predicts a poor prognosis in gastric adenocarcinoma.
abstract: BACKGROUND
  The deubiquitinating enzyme OTUB1 participates in multiple cellular processes. However, its expression and functions in gastric adenocarcinoma remains unknown. The aim of this study was to investigate the expression of OTUB1 and its biological role in gastric adenocarcinoma.
  
  
  METHODS
  We used immunohistochemistry to analyze OTUB1 expressions levels in 80 paired samples of gastric adenocarcinoma and adjacent normal tissue (ANT) and 30 samples of intraepithelial neoplasia (IN). We also analyzed the correlation between OTUB1 expression and clinicopathological parameters and patient survival status. Moreover, we performed wound-healing, transwell, RT-qPCR and Western blot assays to evaluate the impact of OTUB1 on tumor migration and invasion.
  
  
  RESULTS
  In gastric adenocarcinomas, staining for OTUB1 was localized in the cytoplasm. The proportion of samples that expressed OTUB1 and the intensity of its expression were much higher in gastric adenocarcinoma tissues (61 out of 80, 76.25%) than that in either IN (10 out of 30, 33.33%, p<0.001) or ANT (7 out of 80, 8.75%, p<0.001) samples. In malignant cases, higher expression OTUB1 levels were significantly associated with deeper tumor invasion depths (p=0.02), advanced lymph node status (p=0.008) and TNM stage (p=0.001), lymph duct invasion (p<0.001) and nerve invasion (p=0.013). Univariate and multivariate Cox regression analyses revealed that OTUB1 was an independent risk factor for disease-specific survival but not disease-free survival. In vitro wound-healing and transwell assays showed that OTUB1 overexpression promoted tumor cell migration and invasion in gastric cancer cells.
  
  
  CONCLUSIONS
  OTUB1 contributes to gastric cancer development by enhancing tumor invasiveness. Targeting OTUB1 should be considered in future molecular therapies.
authors.affiliation: Department of Pathology, Fudan University Shanghai Cancer CenterShanghai, 200032, China; Department of Oncology, Fudan University Shanghai Cancer CenterShanghai, 200032, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Weng
authors.affiliation: Department of Pathology, Fudan University Shanghai Cancer CenterShanghai, 200032, China; Department of Oncology, Fudan University Shanghai Cancer CenterShanghai, 200032, China.
authors.forename: Qiongyan
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Fudan University Shanghai Cancer CenterShanghai, 200032, China; Department of Oncology, Fudan University Shanghai Cancer CenterShanghai, 200032, China.
authors.forename: Midie
authors.initials: M
authors.lastname: Xu
authors.affiliation: Department of Pathology, Fudan University Shanghai Cancer CenterShanghai, 200032, China; Department of Oncology, Fudan University Shanghai Cancer CenterShanghai, 200032, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Pathology, Fudan University Shanghai Cancer CenterShanghai, 200032, China; Department of Oncology, Fudan University Shanghai Cancer CenterShanghai, 200032, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Fudan University Shanghai Cancer CenterShanghai, 200032, China; Department of Oncology, Fudan University Shanghai Cancer CenterShanghai, 200032, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Shen
authors.affiliation: Department of Pathology, Obstetrics and Gynecology Hospital of Fudan University Shanghai, 200011, China.
authors.forename: Xiaochen
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Pathology, Obstetrics and Gynecology Hospital of Fudan University Shanghai, 200011, China.
authors.forename: Yiqin
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pathology, Fudan University Shanghai Cancer CenterShanghai, 200032, China; Department of Oncology, Fudan University Shanghai Cancer CenterShanghai, 200032, China.
authors.forename: Weiqi
authors.initials: W
authors.lastname: Sheng
keywords: OTUB1; gastric adenocarcinoma; invasion; prognosis