CDKN3 expression is an independent prognostic factor and associated with advanced tumor stage in nasopharyngeal carcinoma

Int J Med Sci. 2018 Jun 14;15(10):992-998. doi: 10.7150/ijms.25065. eCollection 2018.

Abstract

Background: Through data mining from the public transcriptome of NPC, cyclin-dependent kinase inhibitor 3 (CDKN3) was identified as a significantly upregulated gene in NPC. CDKN3 functions as a key factor in cell cycle regulation. This study was aimed to investigate the expression of CDKN3 in NPC tissues and its prognostic significance. Methods: Immunohistochemistry was performed for 124 NPC patients to assess the protein expression of CDKN3. The stainings of CDKN3 were scored by using H-score method. The relationships between CDKN3 expression status and clinicopathological parameters, disease-specific survival (DSS), distant metastasis-free survival (DMeFS), and local recurrence-free survival (LRFS) were statistically analyzed. Results: High expression of CDKN3 was significantly associated with higher primary nodal status (P=0.030) and higher TNM stage (P=0.019). In univariate analysis, high expression of CDKN3 predicted worse DSS (P<0.0001), DMeFS (P<0.0001), and LRFS (P<0.0001). In multivariate analysis, CDKN3 overexpression still acted as an independent prognostic factor for worse DSS (P<0.001; hazard ratio [HR]=11.999, 95% CI: 5.378-26.771), DMeFS (P<0.001; HR=15.069, 95% CI: 5.884-38.592), and LRFS (P<0.001; HR=5.000, 95% CI: 2.312-10.815). Conclusion: High expression of CDKN3 was an independent negative prognostic factor for NPC and was associated with advanced disease status. It might serve as potential therapeutic target and aid in risk stratification for patients with NPC.

Keywords: CDKN3; NPC; cell cycle; nasopharyngeal carcinoma; transcriptome.

MeSH terms

  • Biomarkers, Tumor / metabolism*
  • Carcinoma
  • Cyclin-Dependent Kinase Inhibitor Proteins / metabolism*
  • Dual-Specificity Phosphatases / metabolism*
  • Female
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Nasopharyngeal Carcinoma / metabolism*
  • Nasopharyngeal Carcinoma / pathology
  • Nasopharyngeal Neoplasms / metabolism*
  • Nasopharyngeal Neoplasms / pathology
  • Neoplasm Staging
  • Prognosis

Substances

  • Biomarkers, Tumor
  • Cyclin-Dependent Kinase Inhibitor Proteins
  • CDKN3 protein, human
  • Dual-Specificity Phosphatases