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Title[redir]:
RARβ2 hypermethylation is associated with poor recurrence-free survival in never-smokers with adenocarcinoma of the lung | Clinical Epigenetics | Full Text
Description:
Background This study was aimed at investigating if the effect of RARβ2 hypermethylation on recurrence-free survival (RFS) in non-small cell lung cancer (NSCLC) depends on one’s smoking status and specific interacting proteins. Results We retrospectively analyzed the expressions of five proteins using immunohistochemistry in archival formalin-fixed and paraffin-embedded tissues from 578 NSCLC patients who had undergone surgical resection from 1994 through 2004. Promoter methylation of RARβ2 was assessed by bisulfite pyrosequencing. Recurrence was found in 268 (46%) of 578 NSCLCs with a median follow-up period of 4.8 years. Overexpression of β-catenin, c-MET, cyclin D1, and EGFR occurred in 55%, 72%, 51%, and 41% of the patients, respectively. E-cadherin expression was negative in 62% of the patients, and RARβ2 hypermethylation was found in 37%. The abnormal expression of c-MET (P = 0.002) and EGFR (P = 0.001) was found to be highly prevalent in never-smokers. RARβ2 hypermethylation was significantly associated with poor recurrence-free survival (RFS) in 128 never-smokers with adenocarcinoma (P = 0.01) For parsimonious model building, the five proteins were clustered into three groups (β-catenin and E-cadherin; c-MET; cyclin D1 and EGFR) by an unsupervised hierarchical clustering and were included in a multivariate analysis. Cox proportional hazard analysis showed that RARβ2 hypermethylation was significantly associated with poor RFS in 128 never-smokers with adenocarcinoma (adjusted hazard ratio [HR] = 2.19, 95% confidence interval [CI] = 1.28 to 3.47; P = 0.009), after adjusting for interacting proteins. Conclusions The present study suggests that RARβ2 hypermethylation may be an independent prognostic factor of RFS in never-smokers with adenocarcinoma of the lung.
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Keywords {🔍}
rarβ, cancer, expression, neversmokers, hypermethylation, proteins, lung, rfs, adenocarcinoma, article, google, scholar, egfr, levels, pubmed, cyclin, cells, cell, acid, methylation, recurrence, βcatenin, retinoic, cas, effect, tissues, patients, figure, study, analyzed, ecadherin, analysis, cmet, nsclc, found, kim, lee, tumor, staining, data, survival, eversmokers, status, growth, compared, test, poor, smoking, showed, factor,
Topics {✒️}
formalin-fixed paraffin-embedded tissue beta-catenin/lef-tcf pathway node-negative stage i-ii 578 formalin-fixed paraffin-embedded kaplan-meier survival curves kaplan-meier survival curve reduce inter-observer variability randomized placebo-controlled trial methods study population full size image duk-hwan kim eun yoon cho wilcoxon rank-sum test poor inter-rater reliability methylation-specific pcr technique 10-μm-thick sections state privacy rights lung cancer-derived cells small-cell lung cancer quantitative reverse transcription-pcr beta-catenin protein stability bo bin lee abbreviations rfs e-cadherin/catenin complex real-time pcr poor recurrence-free survival β-catenin-lef/tcf privacy choices/manage cookies paraffin-embedded tissues archival formalin-fixed cut formalin-fixed authors scientific editing bmc β-catenin/tcf signaling [13] prospective large-scale studies wnt/β-catenin signaling south san francisco nuclear β-catenin interacts national research foundation springer nature ubiquitin-proteasome pathway [17] smoker cancer-related death small sample size samsung medical center pyromark pcr kit 9-cis-retinoic acid [9] 9-cis-retinoic acid post-operative follow breast cancer cells
Questions {❓}
- Is it reasonable to recommend the intake of retinoids for the chemoprevention of recurrence in never-smokers who have undergone surgical resection for NSCLC?
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headline:RARβ2 hypermethylation is associated with poor recurrence-free survival in never-smokers with adenocarcinoma of the lung
description:This study was aimed at investigating if the effect of RARβ2 hypermethylation on recurrence-free survival (RFS) in non-small cell lung cancer (NSCLC) depends on one’s smoking status and specific interacting proteins. We retrospectively analyzed the expressions of five proteins using immunohistochemistry in archival formalin-fixed and paraffin-embedded tissues from 578 NSCLC patients who had undergone surgical resection from 1994 through 2004. Promoter methylation of RARβ2 was assessed by bisulfite pyrosequencing. Recurrence was found in 268 (46%) of 578 NSCLCs with a median follow-up period of 4.8 years. Overexpression of β-catenin, c-MET, cyclin D1, and EGFR occurred in 55%, 72%, 51%, and 41% of the patients, respectively. E-cadherin expression was negative in 62% of the patients, and RARβ2 hypermethylation was found in 37%. The abnormal expression of c-MET (P = 0.002) and EGFR (P = 0.001) was found to be highly prevalent in never-smokers. RARβ2 hypermethylation was significantly associated with poor recurrence-free survival (RFS) in 128 never-smokers with adenocarcinoma (P = 0.01) For parsimonious model building, the five proteins were clustered into three groups (β-catenin and E-cadherin; c-MET; cyclin D1 and EGFR) by an unsupervised hierarchical clustering and were included in a multivariate analysis. Cox proportional hazard analysis showed that RARβ2 hypermethylation was significantly associated with poor RFS in 128 never-smokers with adenocarcinoma (adjusted hazard ratio [HR] = 2.19, 95% confidence interval [CI] = 1.28 to 3.47; P = 0.009), after adjusting for interacting proteins. The present study suggests that RARβ2 hypermethylation may be an independent prognostic factor of RFS in never-smokers with adenocarcinoma of the lung.
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headline:RARβ2 hypermethylation is associated with poor recurrence-free survival in never-smokers with adenocarcinoma of the lung
description:This study was aimed at investigating if the effect of RARβ2 hypermethylation on recurrence-free survival (RFS) in non-small cell lung cancer (NSCLC) depends on one’s smoking status and specific interacting proteins. We retrospectively analyzed the expressions of five proteins using immunohistochemistry in archival formalin-fixed and paraffin-embedded tissues from 578 NSCLC patients who had undergone surgical resection from 1994 through 2004. Promoter methylation of RARβ2 was assessed by bisulfite pyrosequencing. Recurrence was found in 268 (46%) of 578 NSCLCs with a median follow-up period of 4.8 years. Overexpression of β-catenin, c-MET, cyclin D1, and EGFR occurred in 55%, 72%, 51%, and 41% of the patients, respectively. E-cadherin expression was negative in 62% of the patients, and RARβ2 hypermethylation was found in 37%. The abnormal expression of c-MET (P = 0.002) and EGFR (P = 0.001) was found to be highly prevalent in never-smokers. RARβ2 hypermethylation was significantly associated with poor recurrence-free survival (RFS) in 128 never-smokers with adenocarcinoma (P = 0.01) For parsimonious model building, the five proteins were clustered into three groups (β-catenin and E-cadherin; c-MET; cyclin D1 and EGFR) by an unsupervised hierarchical clustering and were included in a multivariate analysis. Cox proportional hazard analysis showed that RARβ2 hypermethylation was significantly associated with poor RFS in 128 never-smokers with adenocarcinoma (adjusted hazard ratio [HR] = 2.19, 95% confidence interval [CI] = 1.28 to 3.47; P = 0.009), after adjusting for interacting proteins. The present study suggests that RARβ2 hypermethylation may be an independent prognostic factor of RFS in never-smokers with adenocarcinoma of the lung.
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