| Title | Cohypermethylation of p16 and FHIT promoters as a prognostic factor of recurrence in surgically resected stage I non-small cell lung cancer. | | Author(s) | Kim JS, Kim JW, Han J, Shim YM, Park J, Kim DH | | Institution | Center for Genome Research, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Ilwon-dong, Seoul, Republic of Korea. | | Source | Cancer Res 2006 Apr 15; 66(8):4049-54. | | MeSH | Acid Anhydride Hydrolases
Carcinoma, Non-Small-Cell Lung
DNA Methylation
Female
Genes, p16
Humans
Logistic Models
Lung Neoplasms
Male
Middle Aged
Neoplasm Proteins
Neoplasm Recurrence, Local
Neoplasm Staging
Prognosis
Promoter Regions (Genetics)
Proportional Hazards Models
Research Support, Non-U.S. Gov't
Survival Rate
Tumor Markers, Biological
| | Abstract | Despite advances in the detection and treatment of lung cancer, the prognosis for patients with lung cancer is poor, partly as a result of recurrences. We retrospectively analyzed the relationship between recurrence and survival in patients with non-small cell lung cancers (NSCLC), and the promoter methylation of p16, GSTP1, FHIT, H-cadherin, and RARbeta2 genes to identify a prognostic molecular marker associated with the recurrence of NSCLC. Methylation status from 335 paraffin blocks was determined by methylation-specific PCR. Of the 335 NSCLC samples, promoter methylation was detected in 35% for p16, 39% for RARbeta2, 42% for H-cadherin, 7% for GSTP1, and 21% for FHIT. Recurrence was observed in 39% (132 of 335) of the patients. Recurrence was significantly associated with histology (P = 0.001) and pathologic stage (P = 0.009). Hypermethylation of any single gene was not associated with recurrence in patients. However, cohypermethylation of p16 and FHIT genes in stage I NSCLCs was associated with an increased risk of recurrence [odds ratio, 6.43; 95% confidence interval (CI), 1.04-20.19; P = 0.02] and poor recurrence-free survival after surgery (hazard ratio, 2.03; 95% CI, 1.09-6.23; P = 0.02). In addition, their survival after recurrence was also 4.62 times poorer (95% CI, 1.27-16.48; P = 0.005) than for those without cohypermethylation of both genes. In conclusion, the present study suggests that cohypermethylation of p16 and FHIT genes in patients with stage I NSCLC may be a valuable biomarker for predicting the recurrence-associated prognosis of the disease. | | Language | eng | | Pub Type(s) | Journal Article
| | PubMed ID | 16618724 |
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