Downregulation of TESTIN and its association with cancer history and a tendency toward poor survival in head and neck squamous cell carcinoma

Arch Otolaryngol Head Neck Surg. 2009 Mar;135(3):254-60. doi: 10.1001/archoto.2008.560.

Abstract

Objective: To examine the role of TESTIN as a candidate tumor suppressor gene in head and neck carcinogenesis.

Design: Mutation and messenger RNA (mRNA) expression analyses.

Setting: Academic research.

Patients: Paired normal and tumor samples were obtained from 38 patients with primary head and neck squamous cell carcinoma.

Main outcome measures: Analysis and comparison of TESTIN gene mRNA expression and its relationship to clinicopathologic variables.

Results: Mutation analysis showed a nucleotide and amino acid change in 6 of the 38 tumor samples (16.0%). Semiquantitative mRNA expression analysis of TESTIN revealed a decreased expression in approximately 50% of the tumors compared with their matched normal controls. Interestingly, comparison of clinicopathologic variables to mRNA expression status of TESTIN revealed a significant difference in terms of cancer history (P = .03). Moreover, a higher smoking ratio and a family cancer history were also associated with downregulation of TESTIN, although the difference was not statistically significant (P = .43 and P = .16, respectively). Kaplan-Meier survival analysis demonstrated a worse survival rate among the patients with low TESTIN expression compared with the patients with normal-high TESTIN expression.

Conclusions: Our findings suggest that inactivation of TESTIN is involved in head and neck carcinogenesis through its downregulation. Further studies in various human cancer tissues using a large sample size and in vitro functional studies as well as clinical comparison research studies would give us a better evaluation of TESTIN's role and its possible future application in molecular diagnosis and treatment of different cancer types, including head and neck squamous cell carcinoma.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / pathology
  • Cytoskeletal Proteins
  • DNA Mutational Analysis
  • Disease Progression
  • Down-Regulation*
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Head and Neck Neoplasms / genetics*
  • Head and Neck Neoplasms / mortality
  • Head and Neck Neoplasms / pathology
  • Homeodomain Proteins / genetics*
  • Homeodomain Proteins / metabolism
  • Humans
  • Japan / epidemiology
  • LIM Domain Proteins
  • Male
  • Middle Aged
  • Mutation
  • Prognosis
  • RNA, Neoplasm / genetics*
  • RNA, Neoplasm / metabolism
  • RNA-Binding Proteins
  • Retrospective Studies
  • Reverse Transcriptase Polymerase Chain Reaction
  • Survival Rate
  • Tumor Suppressor Proteins / genetics*
  • Tumor Suppressor Proteins / metabolism

Substances

  • Cytoskeletal Proteins
  • Homeodomain Proteins
  • LIM Domain Proteins
  • RNA, Neoplasm
  • RNA-Binding Proteins
  • TES protein, human
  • Tumor Suppressor Proteins