PMID- 26617874 OWN - NLM STAT- MEDLINE DCOM- 20161213 LR - 20220330 IS - 1936-2625 (Electronic) IS - 1936-2625 (Linking) VI - 8 IP - 9 DP - 2015 TI - Down-regulation of PAX6 by promoter methylation is associated with poor prognosis in non small cell lung cancer. PG - 11452-7 AB - BACKGROUND: Promoter methylation is an alternative mechanism of gene silencing in human tumorigenesis. Although a number of methylated genes have been found in non small cell lung cancer (NSCLC), useful methylation markers for early prognostic evaluation of NSCLC remain largely unknown. METHODS: Using methylation-specific PCR (MSP), we examined promoter methylation status of PAX6 gene, and explored their association with clinical features in NSCLC via chi-square test. NSCLC patient survival was assessed by Kaplan-Meier analyses and a Cox proportional hazard model was employed for multivariate analyses. RESULTS: The methylation level of PAX6 gene was higher in tumor tissues than that in normal tissues. In addition, PAX6 promoter methylation showed a very significant correlation with differentiation (P = 0.002), distant metastasis (P = 0.024), and TNM stage (P = 0.002). PAX6 gene promoter hyper-methylation was found to be significantly associated with poor overall survival (P = 0.018) and to serve as an independent marker for prognosis using multivariate Cox regression analysis (HR: 2.254, 95% CI: 1.088-4.667, P = 0.029). CONCLUSION: We found that PAX6 gene was specifically methylated in NSCLC, and demonstrated the effect of promoter methylation of PAX6 gene on clinical outcome in NSCLC, indicating the methylated PAX6 may be useful biomarkers for prognostic evaluation in NSCLC. FAU - Zhang, Xiangxian AU - Zhang X AD - Xiangya Hospital of Central South University China. FAU - Yang, Xiao AU - Yang X AD - Xiangya Hospital of Central South University China. FAU - Wang, Junling AU - Wang J AD - Department of Seven-year Clinical Medicine, Grade 2011, Zhengzhou University China. FAU - Liang, Tiansong AU - Liang T AD - Radiotherapy and Severe Tumor Institution, Zhengzhou University China. FAU - Gu, Yue AU - Gu Y AD - Department III of Radiation Oncology, The First Affiliated Hospital of Zhengzhou University China. FAU - Yang, Daoke AU - Yang D AD - Department III of Radiation Oncology, The First Affiliated Hospital of Zhengzhou University China. LA - eng PT - Journal Article DEP - 20150901 PL - United States TA - Int J Clin Exp Pathol JT - International journal of clinical and experimental pathology JID - 101480565 RN - 0 (Biomarkers, Tumor) RN - 0 (PAX6 Transcription Factor) RN - 0 (PAX6 protein, human) SB - IM MH - Adult MH - Aged MH - Biomarkers, Tumor/analysis/genetics MH - Carcinoma, Non-Small-Cell Lung/genetics/mortality/*pathology MH - DNA Methylation/*genetics MH - Disease-Free Survival MH - Down-Regulation MH - Female MH - Gene Expression Regulation, Neoplastic/*genetics MH - Humans MH - Kaplan-Meier Estimate MH - Lung Neoplasms/genetics/mortality/*pathology MH - Male MH - Middle Aged MH - PAX6 Transcription Factor/*biosynthesis/genetics MH - Polymerase Chain Reaction MH - Prognosis MH - Promoter Regions, Genetic/genetics MH - Proportional Hazards Models PMC - PMC4637690 OTO - NOTNLM OT - Non-small cell lung cancer OT - PAX6 OT - methylation OT - prognosis EDAT- 2015/12/01 06:00 MHDA- 2016/12/15 06:00 PMCR- 2015/09/01 CRDT- 2015/12/01 06:00 PHST- 2015/04/30 00:00 [received] PHST- 2015/06/22 00:00 [accepted] PHST- 2015/12/01 06:00 [entrez] PHST- 2015/12/01 06:00 [pubmed] PHST- 2016/12/15 06:00 [medline] PHST- 2015/09/01 00:00 [pmc-release] PST - epublish SO - Int J Clin Exp Pathol. 2015 Sep 1;8(9):11452-7. eCollection 2015.