Clinicopathological significance and a potential drugtarget of RARβ in non-small-cell lung carcinoma: a meta-analysis and a systematic review

Figures & data

Figure 1 Schematic flow diagram for selection of included studies.

Table 1 Main characteristics of included studies

Author	Year	Country	Sex (F/M)	Histology (AC/SCC)	Stage (low/advanced)	Smoking (−/+)	Methods	Methylation site
Li et al^Citation44	2014	People’s Republic of China	63/104	81/86	102/65	69/44	MSP	Promoter
Zhao et al^Citation45	2012	People’s Republic of China	12/68	35/45	50/30	19/61	MSP	Promoter
Zhang et al^Citation46	2011	People’s Republic of China	NA	NA	NA	NA	MSP	Promoter
Li et al^Citation40	2014	People’s Republic of China	NA	10/29	34/22	NA	MSP	Promoter
Scesnaite et al^Citation47	2012	Finland	83/129	103/79	35/71	2/104	MSP	Promoter
Yanagawa et al^Citation18	2011	Japan	41/69	NA	44/18	26/36	MSP	Promoter
Liu et al^Citation48	2010	People’s Republic of China	21/59	22/37	60/20	33/47	MSP	Promoter
Hawes et al^Citation49	2010	USA	45/72	51/59	93/24	5/112	Methy light	Promoter
Kubo et al^Citation50	2009	Japan	62/38	NA	52/48	70/30	MSP	Promoter
Umemura et al^Citation33	2008	Japan	1/10	6/4	5/6	2/9	MSP	promoter
Seng et al^Citation51	2008	Australia	84/155	146/92	86/153	NA	MSP	promoter
Hsu et al^Citation52	2007	People’s Republic of China	NA	33/37	48/31	18/56	MSP	promoter
Yanagawa et al^Citation34	2007	Japan	29/72	62/39	33/68	26/36	MSP	promoter
Katayama et al^Citation53	2007	Japan	10/24	32/1	0/34	NA	MSP	promoter
Kim et al^Citation39	2005	Korea	NA	NA	NA	NA	MSP	promoter
Kim et al^Citation43	2005	Korea	NA	42/27	31/30	NA	MSP	promoter
Tomizawa et al^Citation17	2004	Japan	43/77	45/72	32/86	29/61	MSP	Promoter
Topaloglu et al^Citation54	2004	USA	NA	21/7	26/5	NA	Real-time PCR	Promoter

Abbreviations: F, female; M, male; AC, adenocarcinoma; SCC, squamous cell carcinoma; MSP, methylation-specific PCR; PCR, polymerase chain reaction; NA, not available.

Figure 2 Forest plot for RARβ hypermethylation in NSCLC and non-neoplastic lung tissue.

Abbreviations: NSCLC, non-small-cell lung carcinoma; CI, confidence interval; df, degree of freedom; M–H, Mantel–Haenszel.

Figure 3 Forest plot for RARβ hypermethylation in AC and SCC.

Abbreviations: AC, adenocarcinoma; SCC, squamous cell carcinoma; CI, confidence interval; df, degree of freedom; M–H, Mantel–Haenszel.

Figure 4 Forest plot for RARβ hypermethylation in advanced and low stage of NSCLC.

Abbreviations: NSCLC, non-small-cell lung carcinoma; CI, confidence interval; df, degree of freedom; M–H, Mantel–Haenszel.

Figure 5 Forest plot for RARβ hypermethylation of NSCLC in smoking and nonsmoking individual.

Abbreviations: NSCLC, non-small-cell lung carcinoma; CI, confidence interval; df, degree of freedom; M–H, Mantel–Haenszel.

Figure 6 Forest plot for RARβ hypermethylation of NSCLC in different sexes.

Abbreviations: NSCLC, non-small-cell lung carcinoma; CI, confidence interval; df, degree of freedom; M–H, Mantel–Haenszel.

Figure 7 Forest plot for the association between RARβ hypermethylation and risk of NSCLC.

Abbreviations: NSCLC, non-small-cell lung carcinoma; CI, confidence interval; df, degree of freedom; SE, standard error of the mean.

Figure 8 Funnel plot for publication bias.

Notes: (A) RARβ hypermethylation in NSCLC and non-neoplastic lung tissue; (B) RARβ hypermethylation in AC and SCC; (C) RARβ hypermethylation in advanced and low stage of NSCLC; (D) RARβ hypermethylation of NSCLC in smoking and nonsmoking individual; (E) RARβ hypermethylation of NSCLC in different sexes; (F) the association between RARβ hypermethylation and the risk of NSCLC.
Abbreviations: NSCLC, non-small-cell lung carcinoma; AC, adenocarcinoma; SCC, squamous cell carcinoma; SE, standard error of the mean; OR, odds ratio; df, degree of freedom.

LiWDengJWangSSAssociation of methylation of the RAR-beta gene with cigarette smoking in non-small cell lung cancer with Southern-Central Chinese populationAsian Pac J Cancer Prev201415109371094125605205

 PubMedGoogle Scholar

ZhaoXWangNZhangMXueSShiKChenZDetection of methylation of the RAR-beta gene in patients with non-small cell lung cancerOncol Lett2012365465810.3892/ol.2011.527 ol-03-03-0654 [pii]22740970

 PubMed Web of Science ®Google Scholar

ZhangCYJinYTXuHYRelationship between promoter methylation of p16, DAPK and RAR beta genes and the clinical data of non-small cell lung cancerZhonghua Yi Xue Yi Chuan Xue Za Zhi201128232810.3760/cma.j.issn.1003-9406.2011.01.006 940628006 [pii]21287504

 PubMedGoogle Scholar

LiWDengJTangJXCombined effects methylation of FHIT, RASSF1A and RARbeta genes on non-small cell lung cancer in the Chinese populationAsian Pac J Cancer Prev2014155233523725040980

 PubMed Web of Science ®Google Scholar

ScesnaiteAJarmalaiteSMutanenPSimilar DNA methylation pattern in lung tumours from smokers and never-smokers with second-hand tobacco smoke exposureMutagenesis20122742342910.1093/mutage/ger092 ger092 [pii]22217548

 PubMed Web of Science ®Google Scholar

YanagawaNTamuraGOizumiHEndohMSadahiroMMotoyamaTInverse correlation between EGFR mutation and FHIT, RASSF1A and RUNX3 methylation in lung adenocarcinoma: relation with smoking statusAnticancer Res20113112111214 31/4/1211 [pii]21508367

 PubMed Web of Science ®Google Scholar

LiuZLiWLeiZCpG island methylator phenotype involving chromosome 3p confers an increased risk of non-small cell lung cancerJ Thorac Oncol2010579079720521346

 PubMed Web of Science ®Google Scholar

HawesSESternJEFengQDNA hypermethylation of tumors from non-small cell lung cancer (NSCLC) patients is associated with gender and histologic typeLung Cancer20106917217910.1016/j.lungcan.2009.11.002 S0169-5002(09)00579-0 [pii]19945765

 PubMed Web of Science ®Google Scholar

KuboTYamamotoHIchimuraKDNA methylation in small lung adenocarcinoma with bronchioloalveolar carcinoma componentsLung Cancer20096532833210.1016/j.lungcan.2008.12.001 S0169-5002(08)00663-6 [pii]19144441

 PubMed Web of Science ®Google Scholar

UmemuraSFujimotoNHirakiAAberrant promoter hypermethylation in serum DNA from patients with silicosisCarcinogenesis2008291845184910.1093/carcin/bgn169 bgn169 [pii]18632757

 PubMed Web of Science ®Google Scholar

SengTJCurreyNCooperWADLEC1 and MLH1 promoter methylation are associated with poor prognosis in non-small cell lung carcinomaBr J Cancer20089937538210.1038/sj.bjc.66044526604452 pii18594535

 PubMed Web of Science ®Google Scholar

HsuHSChenTPWenCKMultiple genetic and epigenetic biomarkers for lung cancer detection in cytologically negative sputum and a nested case-control study for risk assessmentJ Pathol200721341241910.1002/path.224617973238

 PubMed Web of Science ®Google Scholar

YanagawaNTamuraGOizumiHPromoter hypermethylation of RASSF1A and RUNX3 genes as an independent prognostic prediction marker in surgically resected non-small cell lung cancersLung Cancer200758131138 S0169-5002(07)00315-7 [pii]10.1016/j.lungcan.2007.05.01117606310

 PubMed Web of Science ®Google Scholar

KatayamaHHirakiAAoeKAberrant promoter methylation in pleural fluid DNA for diagnosis of malignant pleural effusionInt J Cancer20071202191219510.1002/ijc.2257617285579

 PubMed Web of Science ®Google Scholar

KimYTParkSJLeeSHPrognostic implication of aberrant promoter hypermethylation of CpG islands in adenocarcinoma of the lungJ Thorac Cardiovasc Surg20051301378 doi:S0022-5223-(05)01052-4 [pii]10.1016/j.jtcvs.2005.06.01516256792

 PubMed Web of Science ®Google Scholar

KimYTLeeSHSungSWKimJHCan aberrant promoter hypermethylation of CpG islands predict the clinical outcome of non-small cell lung cancer after curative resection?Ann Thorac Surg20057911801188 discussion. 1180–1188. doi:S0003-4975(04)02007-7 [pii]10.1016/j.athoracsur.2004.09.06015797047

 PubMed Web of Science ®Google Scholar

TomizawaYIijimaHNomotoTClinicopathological significance of aberrant methylation of RARbeta2 at 3p24, RASSF1A at 3p21.3, and FHIT at 3p14.2 in patients with non-small cell lung cancerLung Cancer200446305312 S0169500204002181 [pii]10.1016/j.lungcan.2004.05.00315541815

 PubMed Web of Science ®Google Scholar

TopalogluOHoqueMOTokumaruYDetection of promoter hypermethylation of multiple genes in the tumor and bronchoalveolar lavage of patients with lung cancerClin Cancer Res2004102284228815073103

 PubMed Web of Science ®Google Scholar