USP9X mRNA expression predicts clinical outcome for esophageal squamous cell carcinoma treated with cisplatin-based therapy

Clin Res Hepatol Gastroenterol. 2020 Nov;44(6):932-938. doi: 10.1016/j.clinre.2019.10.004. Epub 2020 Jan 23.

Abstract

Introduction: Combination therapy with cisplatin is the conventional first-line treatment in patients with locally advanced or metastatic esophageal squamous cell carcinoma (ESCC). Ubiquitin-specific protease 9X (USP9X) has been shown to be associated with resistance to chemotherapy drugs in several cancers. The purpose of this study was to explore the predictive effects of USP9X on advanced ESCC patients treated with cisplatin-based regimens.

Materials and methods: The subjects were 69 advanced ESCC patients who received first-line cisplatin-based chemotherapy or chemoradiotherapy. The quantitative real-time PCR was performed to measure USP9X mRNA expression. The correlation of USP9X expression with clinical parameters and tumor response was analyzed. The Kaplan-Meier method and Cox analysis were employed to analyze differences in overall survival (OS).

Results: USP9X mRNA expression was positively associated with the TMN stage at initial diagnosis. Patients with low USP9X mRNA expression had a significantly higher objective response rate (57.1% vs. 17.6%, P=0.001) and longer median OS (25.0 vs. 14.0 months, P<0.001) than those with high expression in all patients or in different treatment subgroups (all P<0.05). Multivariate analysis showed that low mRNA expression of USP9X emerged as an independent prognostic factor indicating prolonged OS (hazard ratio 0.50, 95% CI 0.34-0.73; P<0.001).

Conclusion: These findings suggest that high USP9X mRNA expression predicts poor clinical efficacy and survival to cisplatin-based therapy in patients with advanced ESCC.

Keywords: Cisplatin; Esophageal squamous cell carcinoma; Predictive factor; USP9X.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / therapy
  • Cisplatin / administration & dosage*
  • Docetaxel / administration & dosage
  • Drug Resistance, Neoplasm / genetics
  • Esophageal Neoplasms / genetics*
  • Esophageal Neoplasms / mortality
  • Esophageal Neoplasms / therapy
  • Female
  • Fluorouracil / administration & dosage
  • Humans
  • Male
  • Middle Aged
  • Prognosis
  • RNA, Messenger / metabolism*
  • Radiotherapy, Adjuvant
  • Ubiquitin Thiolesterase / genetics*

Substances

  • RNA, Messenger
  • USP9X protein, human
  • Docetaxel
  • Ubiquitin Thiolesterase
  • Cisplatin
  • Fluorouracil