Overexpression of chromosome 14 open reading frame 166 correlates with disease progression and poorer prognosis in human NPC

Tumour Biol. 2015 Sep;36(10):7977-86. doi: 10.1007/s13277-015-3518-8. Epub 2015 May 12.

Abstract

Chromosome 14 open reading frame 166 (c14orf166) contributes to regulation of centrosome architecture, transcription initiation, and RNA elongation and processing. However, the role of c14orf166 in human cancer remains unclear. This study aimed to investigate the expression and clinicopathological significance of c14orf166 in nasopharyngeal carcinoma (NPC). Real-time PCR and Western blotting analyses were employed to examine c14orf166 expression in immortalized primary nasopharyngeal epithelial cells (NP69), six NPC cell lines, three paired tumor samples and the adjacent noncancerous tissues from the same patients, and three additional tumor samples. Immunohistochemistry was performed to examine c14orf166 protein expression in archived paraffin-embedded tumor samples from 109 patients with clinicopathologically confirmed NPC. The association of c14orf166 expression with clinicopathological features and survival outcomes was assessed. C14orf166 messenger RNA and protein expression were upregulated in NPC cell lines and human tumor tissues compared to NP69 cells and noncancerous tissue samples, respectively. Immunohistochemical analyses revealed 104/109 (95.4 %) of the NPC tissue samples expressed c14orf166. High expression of c14orf166 (cutoff score >6) was significantly associated with gender (P = 0.016), clinical stage (P = 0.010), T classification (P = 0.013), N classification (P = 0.029), distant metastasis (P < 0.001), vital status (P = 0.001), and treatment method (P = 0.028; chi-square test). High c14orf166 expression was associated with significantly shorter overall survival (OS) and disease-free survival (DFS) than low c14orf166 expression. Multivariate analysis revealed c14orf166 was an independent prognostic indicator of OS and DFS in all patients (P = 0.046, P = 0.006) and was associated with poor OS and DFS in the subgroups with advanced clinical stage (P = 0.037, P = 0.001), lymph node metastasis (P = 0.001, P < 0.001), and T3-T4 disease (P = 0.005, P = 0.001), respectively. C14orf166 is overexpressed and may represent a novel prognostic factor in NPC.

Keywords: C14orf166; Disease-free survival; NPC; Overall survival; Prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / metabolism
  • Blotting, Western
  • Carcinoma
  • Disease Progression
  • Female
  • Follow-Up Studies
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunoenzyme Techniques
  • Male
  • Middle Aged
  • Nasopharyngeal Carcinoma
  • Nasopharyngeal Neoplasms / genetics*
  • Nasopharyngeal Neoplasms / metabolism
  • Nasopharyngeal Neoplasms / mortality
  • Nasopharyngeal Neoplasms / pathology*
  • Neoplasm Staging
  • Prognosis
  • RNA, Messenger
  • Real-Time Polymerase Chain Reaction
  • Survival Rate
  • Trans-Activators / genetics*
  • Trans-Activators / metabolism

Substances

  • Biomarkers, Tumor
  • RNA, Messenger
  • RTRAF protein, human
  • Trans-Activators