Clinicopathological significance and a potential drug target of RARβ in non-small-cell lung carcinoma: a meta-analysis and a systematic review
Xiaoyun Song,* Kang Shi,* Shi-Jie Zhou, Da-Ping Yu, Zhidong Liu, Yi Han Department of Thoracic Surgery, Beijing Chest Hospital, Capital Medical University, Beijing, People’s Republic of China *These authors contributed equally to this work Abstract: Lung cancer is the...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Dove Medical Press
2016-04-01
|
| Series: | Drug Design, Development and Therapy |
| Subjects: | |
| Online Access: | https://www.dovepress.com/clinicopathological-significance-and-a-potential-drug-target-of-rarbet-peer-reviewed-article-DDDT |
| _version_ | 1819064930349875200 |
|---|---|
| author | Song X Shi K Zhou SJ Yu DP Liu Z Han Y |
| author_facet | Song X Shi K Zhou SJ Yu DP Liu Z Han Y |
| author_sort | Song X |
| collection | DOAJ |
| description | Xiaoyun Song,* Kang Shi,* Shi-Jie Zhou, Da-Ping Yu, Zhidong Liu, Yi Han Department of Thoracic Surgery, Beijing Chest Hospital, Capital Medical University, Beijing, People’s Republic of China *These authors contributed equally to this work Abstract: Lung cancer is the leading cause of cancer-related mortality in men worldwide. Aberrant RARβ promoter methylation has been frequently investigated in non-small-cell lung carcinoma (NSCLC), the most common form of lung cancer. The aim of present study was to carry out a meta-analysis and a systematic review to evaluate clinicopathological significance of RARβ promoter hypermethylation in NSCLC. A systematic literature search was carried out. The data were extracted and assessed by two reviewers independently. The Cochrane software Review Manager 5.2 was used to conduct the review. Odds ratios (ORs) with 95% corresponding confidence intervals (CIs) were calculated. A total of 18 relevant articles were available for meta-analysis which included 1,871 participants. The frequency of RARβ hypermethylation was significantly increased in NSCLC than in nonmalignant lung tissue, and the pooled OR was 5.69 (P<0.00001). RARβ hypermethylation was significantly more frequently observed in adenocarcinoma (AC) than in squamous cell carcinoma (SCC), and the pooled OR was 1.47 (P=0.005). Hypermethylation of RARβ gene in NSCLC was 2.46 times higher in smoking than in nonsmoking individuals, and the pooled OR was 2.46 (P=0.0002). RARβ hypermethylation rate was not significantly correlated with stage of the disease and sex. RARβ gene methylation status was not associated with prognosis of patients with NSCLC. In conclusion, RARβ promoter hypermethylation significantly increased in NSCLC than in non-neoplastic lung tissue and is predominant in AC, suggesting that RARβ methylation contributes to the development of NSCLC, especially AC. RARβ gene is a potential novel target for development of personalized therapy in patients with NSCLC, and is promising in restoration of retinoic acid-target gene induction via demethylation of RARβ1' promoter. Keywords: NSCLC, RARβ, methylation, tumor suppressor gene, drug target, RA-resistance, meta-analysis, odds ratio |
| first_indexed | 2024-12-21T15:38:23Z |
| format | Article |
| id | doaj.art-34c608c721714f68a62b346798ebd3d5 |
| institution | Directory Open Access Journal |
| issn | 1177-8881 |
| language | English |
| last_indexed | 2024-12-21T15:38:23Z |
| publishDate | 2016-04-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Drug Design, Development and Therapy |
| spelling | doaj.art-34c608c721714f68a62b346798ebd3d52022-12-21T18:58:34ZengDove Medical PressDrug Design, Development and Therapy1177-88812016-04-012016Issue 11345135426339Clinicopathological significance and a potential drug target of RARβ in non-small-cell lung carcinoma: a meta-analysis and a systematic reviewSong XShi KZhou SJYu DPLiu ZHan YXiaoyun Song,* Kang Shi,* Shi-Jie Zhou, Da-Ping Yu, Zhidong Liu, Yi Han Department of Thoracic Surgery, Beijing Chest Hospital, Capital Medical University, Beijing, People’s Republic of China *These authors contributed equally to this work Abstract: Lung cancer is the leading cause of cancer-related mortality in men worldwide. Aberrant RARβ promoter methylation has been frequently investigated in non-small-cell lung carcinoma (NSCLC), the most common form of lung cancer. The aim of present study was to carry out a meta-analysis and a systematic review to evaluate clinicopathological significance of RARβ promoter hypermethylation in NSCLC. A systematic literature search was carried out. The data were extracted and assessed by two reviewers independently. The Cochrane software Review Manager 5.2 was used to conduct the review. Odds ratios (ORs) with 95% corresponding confidence intervals (CIs) were calculated. A total of 18 relevant articles were available for meta-analysis which included 1,871 participants. The frequency of RARβ hypermethylation was significantly increased in NSCLC than in nonmalignant lung tissue, and the pooled OR was 5.69 (P<0.00001). RARβ hypermethylation was significantly more frequently observed in adenocarcinoma (AC) than in squamous cell carcinoma (SCC), and the pooled OR was 1.47 (P=0.005). Hypermethylation of RARβ gene in NSCLC was 2.46 times higher in smoking than in nonsmoking individuals, and the pooled OR was 2.46 (P=0.0002). RARβ hypermethylation rate was not significantly correlated with stage of the disease and sex. RARβ gene methylation status was not associated with prognosis of patients with NSCLC. In conclusion, RARβ promoter hypermethylation significantly increased in NSCLC than in non-neoplastic lung tissue and is predominant in AC, suggesting that RARβ methylation contributes to the development of NSCLC, especially AC. RARβ gene is a potential novel target for development of personalized therapy in patients with NSCLC, and is promising in restoration of retinoic acid-target gene induction via demethylation of RARβ1' promoter. Keywords: NSCLC, RARβ, methylation, tumor suppressor gene, drug target, RA-resistance, meta-analysis, odds ratiohttps://www.dovepress.com/clinicopathological-significance-and-a-potential-drug-target-of-rarbet-peer-reviewed-article-DDDTNSCLCRAR-betaMethylationTumor suppressor geneDrug targetRA-resistanceMeta-analysisOdds ratio. |
| spellingShingle | Song X Shi K Zhou SJ Yu DP Liu Z Han Y Clinicopathological significance and a potential drug target of RARβ in non-small-cell lung carcinoma: a meta-analysis and a systematic review Drug Design, Development and Therapy NSCLC RAR-beta Methylation Tumor suppressor gene Drug target RA-resistance Meta-analysis Odds ratio. |
| title | Clinicopathological significance and a potential drug target of RARβ in non-small-cell lung carcinoma: a meta-analysis and a systematic review |
| title_full | Clinicopathological significance and a potential drug target of RARβ in non-small-cell lung carcinoma: a meta-analysis and a systematic review |
| title_fullStr | Clinicopathological significance and a potential drug target of RARβ in non-small-cell lung carcinoma: a meta-analysis and a systematic review |
| title_full_unstemmed | Clinicopathological significance and a potential drug target of RARβ in non-small-cell lung carcinoma: a meta-analysis and a systematic review |
| title_short | Clinicopathological significance and a potential drug target of RARβ in non-small-cell lung carcinoma: a meta-analysis and a systematic review |
| title_sort | clinicopathological significance and a potential drug target of rar beta in non small cell lung carcinoma a meta analysis and a systematic review |
| topic | NSCLC RAR-beta Methylation Tumor suppressor gene Drug target RA-resistance Meta-analysis Odds ratio. |
| url | https://www.dovepress.com/clinicopathological-significance-and-a-potential-drug-target-of-rarbet-peer-reviewed-article-DDDT |
| work_keys_str_mv | AT songx clinicopathologicalsignificanceandapotentialdrugtargetofrarbetainnonsmallcelllungcarcinomaametaanalysisandasystematicreview AT shik clinicopathologicalsignificanceandapotentialdrugtargetofrarbetainnonsmallcelllungcarcinomaametaanalysisandasystematicreview AT zhousj clinicopathologicalsignificanceandapotentialdrugtargetofrarbetainnonsmallcelllungcarcinomaametaanalysisandasystematicreview AT yudp clinicopathologicalsignificanceandapotentialdrugtargetofrarbetainnonsmallcelllungcarcinomaametaanalysisandasystematicreview AT liuz clinicopathologicalsignificanceandapotentialdrugtargetofrarbetainnonsmallcelllungcarcinomaametaanalysisandasystematicreview AT hany clinicopathologicalsignificanceandapotentialdrugtargetofrarbetainnonsmallcelllungcarcinomaametaanalysisandasystematicreview |