Down regulation of high in normal-1 (HIN-1) is a frequent event in stage I non-small cell lung cancer and correlates with poor clinical outcome

Clin Cancer Res. 2004 Feb 15;10(4):1338-43. doi: 10.1158/1078-0432.ccr-1174-03.

Abstract

Purpose: The aim of this study was to evaluate the prevalence and the clinical significance of HIN-1 mRNA expression in early stage non-small cell lung carcinomas (NSCLCs).

Experimental design: A series of 91 NSCLC patients with stage I neoplastic disease was studied. HIN-1 expression was investigated by quantitative real-time reverse transcription-PCR on tumor specimens and matching normal lung tissues. Variables were analyzed by chi(2) test and Fisher's exact tests. Survival was evaluated with the method of Kaplan-Meier. Multivariate analysis was performed with Cox's proportional hazards model.

Results: Seventy one (78%) tumors showed a reduction of HIN-1 mRNA compared with the normal counterpart. The range of reduction varied greatly, from -2-fold to -3350-fold. Setting a cutoff at -46-fold (median value of HIN-1 mRNA reduction), 46 cases (51%) had a markedly reduced expression, and 45 cases (49%) showed a normal or slightly reduced expression. A statistically significant association between low HIN-1 mRNA levels and T status was observed (P = 0.036). Univariate survival curves, estimated using the method of Kaplan-Meier, defined a significant association between HIN-1 expression and both overall survival (P = 0.0095) and disease-free survival (P = 0.0122). A multivariate analysis, performed by Cox's proportional hazards regression model, confirmed that a low HIN-1 expression was the only significant factor to predict poor prognosis.

Conclusions: Our data indicate that HIN-1 expression, measured by real-time reverse transcription-PCR, is a possible prognostic factor in patients with stage I NSCLC. Additional studies are required to further validate this potential prognostic marker.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Cytokines / biosynthesis*
  • DNA Primers / pharmacology
  • DNA, Complementary / metabolism
  • Disease-Free Survival
  • Down-Regulation*
  • Female
  • Humans
  • Lung / pathology
  • Lung Neoplasms / metabolism*
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Polymerase Chain Reaction
  • Prognosis
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Time Factors
  • Treatment Outcome
  • Tumor Suppressor Proteins / biosynthesis*

Substances

  • Biomarkers, Tumor
  • Cytokines
  • DNA Primers
  • DNA, Complementary
  • RNA, Messenger
  • SCGB3A1 protein, human
  • Tumor Suppressor Proteins