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


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.
Hayashi
M
M
Laboratory of Cancer Diagnosis and Therapy, Saitama Cancer Center Research Institute, Saitama, Japan.
Tokuchi
Y
Y
Hashimoto
T
T
Hayashi
S
S
Nishida
K
K
Ishikawa
Y
Y
Nakagawa
K
K
Tsuchiya
S
S
Okumura
S
S
Tsuchiya
E
E
D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000401:mortality; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D016147:Genes, Tumor Suppressor; D006801:Humans; D051741:Kruppel-Like Transcription Factors; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis; D012334:RNA, Neoplasm / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis; D014157:Transcription Factors / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D016896:Treatment Outcome; D016335:Zinc Fingers / Q000235:genetics
D004273:DNA, Neoplasm; C096870:Hic1 protein, mouse; D051741:Kruppel-Like Transcription Factors; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D014157:Transcription Factors