Reduced HIC-1 gene expression in non-small cell lung cancer and its clinical significance

Anticancer Res. Jan-Feb 2001;21(1B):535-40.

Abstract

Background: HIC-1 (hypermethylated in cancer-1) is a candidate tumor suppressor gene, identified in a region of frequent loss of heterozygosity on chromosome 17p13.3, which is telomeric from TP53 and often deleted in surgically resected lung cancers. To determine the significance of HIC-1 in lung cancer, we assessed its expression status and prognostic association in 47 adenocarcinomas and squamous cell carcinomas.

Materials and methods: RNA was extracted from tumors and corresponding normal tissues of surgically resected lungs, and the amount of HIC-1 mRNA was determined by means of semi-quantitative reverse transcriptase-polymerase chain reaction.

Results: HIC-1 expression in tumors was less than that in normal lung tissues in 40 of 47 patients (85%), indicating frequent partial silencing. Median tumor/normal lung tissue (T/L) ratios for HIC-1 expression were 0.51 and 0.75 for adenocarcinomas and squamous cell carcinomas, respectively. No significant difference of median T/L ratio was observed between the two histological types, or among clinical stages of the patients. However, the reduced expression of HIC-1 gene in the tumor had a direct link with the clinical outcome: lower T/L ratios (< 0.5) were significantly associated with short survival (P = 0.034), an association also observed in cases restricted to stage I (P = 0.047).

Conclusions: The results suggest that low HIC-1 expression is involved in malignant progression of non-small cell lung cancer.

Publication types

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

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / mortality
  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / mortality
  • Chromosomes, Human, Pair 17 / genetics
  • DNA Methylation
  • DNA, Neoplasm / genetics
  • DNA, Neoplasm / metabolism
  • Disease Progression
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Gene Silencing
  • Genes, Tumor Suppressor
  • Humans
  • Kruppel-Like Transcription Factors
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / mortality
  • Male
  • Middle Aged
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / deficiency*
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / physiology
  • RNA, Messenger / biosynthesis
  • RNA, Neoplasm / biosynthesis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Survival Analysis
  • Transcription Factors / biosynthesis
  • Transcription Factors / deficiency*
  • Transcription Factors / genetics
  • Transcription Factors / physiology
  • Treatment Outcome
  • Zinc Fingers / genetics

Substances

  • DNA, Neoplasm
  • Hic1 protein, mouse
  • Kruppel-Like Transcription Factors
  • Neoplasm Proteins
  • RNA, Messenger
  • RNA, Neoplasm
  • Transcription Factors