Expression of SESN1, UHRF1BP1, and miR-377-3p as prognostic markers in mutated TP53 squamous cell carcinoma of the head and neck

Cancer Biol Ther. 2017 Oct 3;18(10):775-782. doi: 10.1080/15384047.2017.1373212. Epub 2017 Sep 8.

Abstract

The tumor suppressor gene TP53 is the most frequently mutated gene in human papillomavirus (HPV)-negative head and neck squamous cell carcinoma (HNSCC). It represents a known transcription factor that controls different microRNAs (miRNA) and target genes involved in the regulation of cellular stress, apoptosis and response to DNA damage. We used The Cancer Genome Atlas database to investigate the difference in transcriptome and proteome levels between mutated and wild-type TP53 HPV-negative HNSCC. Using different databases and an extensive literature review, we built the transcriptional and post-transcriptional network regulated by TP53. TP53 mutation was associated with poor overall survival in 203 HPV-negative patients compared to 40 patients with TP53 wild-type tumors. Using the enrichment analysis, we found that UHRF1BP1 and SESN1 mRNA were linked to prognosis in the TP53 mutated group. This is also the case for miR-377-3p, an important miRNA regulator of SESN1. Our study shows that SESN1 mRNA, UHRF1BP11 mRNA and miRNA-377-3p levels are prognostically relevant in HPV-negative HNSCC patients. This finding may help with patient stratification and the development of potential new therapeutic targets to treat patients with HNSCC.

Keywords: HPV negative; Head neck squamous cell carcinoma; TP53 regulatory network; enrichment analysis; miRNA regulators; overall survival; prognostic relevance.

Publication types

  • Review

MeSH terms

  • Aged
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / mortality
  • Computational Biology
  • Datasets as Topic
  • Down-Regulation
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Gene Regulatory Networks / genetics
  • Head and Neck Neoplasms / genetics*
  • Head and Neck Neoplasms / mortality
  • Heat-Shock Proteins / genetics*
  • Heat-Shock Proteins / metabolism
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Mutation
  • Prognosis
  • RNA, Messenger / metabolism
  • Risk Assessment / methods
  • Squamous Cell Carcinoma of Head and Neck
  • Tumor Suppressor Protein p53 / genetics*
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Heat-Shock Proteins
  • MIRN377 microRNA, human
  • MicroRNAs
  • RNA, Messenger
  • SESN1 protein, human
  • TP53 protein, human
  • Tumor Suppressor Protein p53