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

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 investigat...

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Published in:Clinical cancer research 2004-02, Vol.10 (4), p.1338-1343
Main Authors: MARCHETTI, Antonio, BARASSI, Fabio, MARTELLA, Carla, CHELLA, Antonio, SALVATORE, Simona, CASTRATARO, Antonio, MUCILLI, Felice, SACCO, Rocco, BUTTITTA, Fiamma
Format: Article
Language:English
Subjects:
Adult
Aged
Antineoplastic agents
Biological and medical sciences
Biomarkers, Tumor
Carcinoma, Non-Small-Cell Lung - metabolism
Cytokines - biosynthesis
Disease-Free Survival
DNA Primers - pharmacology
DNA, Complementary - metabolism
Down-Regulation
Female
Humans
Lung - pathology
Lung Neoplasms - metabolism
Male
Medical sciences
Middle Aged
Multivariate Analysis
Pharmacology. Drug treatments
Polymerase Chain Reaction
Prognosis
Reverse Transcriptase Polymerase Chain Reaction
RNA, Messenger - metabolism
Time Factors
Treatment Outcome
Tumor Suppressor Proteins - biosynthesis
Tumors
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Summary: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 χ 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.
ISSN:1078-0432
1557-3265
DOI:10.1158/1078-0432.CCR-1174-03