Cancer Medicine (Jun 2020)

Prognostic and predicted significance of Ubqln2 in patients with hepatocellular carcinoma

  • Yuan‐Deng Luo,
  • Hong‐Qiang Yu,
  • Xiao‐Yu Liu,
  • Deng Huang,
  • Hai‐Su Dai,
  • Lei Fang,
  • Yu‐Jun Zhang,
  • Jie‐Juan Lai,
  • Yan Jiang,
  • Ling Shuai,
  • Lei‐Da Zhang,
  • Geng Chen,
  • Ping Bie,
  • Chuan‐Ming Xie

DOI
https://doi.org/10.1002/cam4.3040
Journal volume & issue
Vol. 9, no. 12
pp. 4083 – 4094

Abstract

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Abstract Purpose Hepatocellular carcinoma (HCC) is a common malignant cancer and the third leading cause of death worldwide. The molecular mechanism of HCC remains unclear. Recent studies have demonstrated that the ubiquitin‐proteasome system (UPS) is associated with HCC. Ubqln2, a member of the UPS, is abnormally expressed in HCC. However, whether Ubqln2 is associated with HCC prognosis remains unknown. Patients and Methods We analyzed the associations between overall survival and various risk factors in 355 HCC tissue samples obtained from the Cancer Genomic Atlas (TCGA) database at the mRNA level and in 166 HCC tissue samples from Southwest Hospital at the protein level. qRCR was used to determinate Ubqln2 expression in cancer and noncancerous tissues. The association between Ubqln2 and Ki‐67 was analyzed by immunohistochemistry. The association between Ubqln2 expression and survival was analyzed using Kaplan‐Meier curve and Cox proportional hazards models. A nomogram was used to predict the impact of Ubqln2 on prognosis. Mutated genes were analyzed to determine the potential mechanism. Results Ubqln2 highly expressed in HCC tissues. The Ubqln2 mRNA level had significant relations with UICC tumor stage (P = .022), UICC stage (P = .034) and resection potential (P = .017). Concordantly, the Ubqln2 protein was closely associated with tumor size (P = .005), UICC stage (P = .012), and recurrence (P = .009). Ubqln2 was highly expressed in HCC and positively associated with poor survival. The nomogram precisely predicted the prognosis of HCC patients with high or low Ubqln2 expression. A genomic waterfall plot suggested that Ubqln2 expression was closely associated with mutated CTNNB1. Conclusion Our findings reveal that Ubqln2, an independent risk factor for HCC, is a potential prognostic marker in HCC patients. Ubqln2 expression is positively associated with mutated CTNNB1.

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