- Volume 14 Issue 6
DOI QR Code
Associations Between RASSF1A Promoter Methylation and NSCLC: A Meta-analysis of Published Data
- Liu, Wen-Jian (Department of Chemotherapy, The Affiliated Tumor Hospital of Guangxi Medical University) ;
- Tan, Xiao-Hong (Department of Chemotherapy, The Affiliated Tumor Hospital of Guangxi Medical University) ;
- Guo, Bao-Ping (Department of Chemotherapy, The Affiliated Tumor Hospital of Guangxi Medical University) ;
- Ke, Qing (Department of Chemotherapy, The Affiliated Tumor Hospital of Guangxi Medical University) ;
- Sun, Jie (Department of Chemotherapy, The Affiliated Tumor Hospital of Guangxi Medical University) ;
- Cen, Hong (Department of Chemotherapy, The Affiliated Tumor Hospital of Guangxi Medical University)
- Published : 2013.06.30
Background: RASSF1A has been reported to be a candidate tumor suppressor in non-small cell lung cancer (NSCLC). However, the association between RASSF1A promoter methylation and NSCLC remains unclear, particularly in regarding links to clinicopathologic features. Methods: Eligible studies were identified through searching PubMed, EMBASE, Cochrane Library and China National Knowledge Infrastructure (CNKI) databases. Studies were pooled and odds ratios (ORs) with corresponding confidence intervals (CIs) were calculated. Funnel plots were also performed to evaluate publication bias. Results: Nineteen studies involving 2,063 cases of NSCLC and 1,184 controls were included in this meta-analysis. A significant association was observed between RASSF1A methylation and NSCLC in the complete data set (OR = 19.42, 95% CI: 14.04-26.85, P < 0.001). Pooling the control tissue subgroups (heterogeneous/autologous) gave pooled ORs of 32.4 (95% CI, 12.4-84.5) and 17.7 (95% CI, 12.5-25.0) respectively. Racial subgroup (Caucasian/Asian) analysis gave pooled ORs of 26.6 (95% CI, 10.9-64.9) and 20.9 (95% CI, 14.4-30.4) respectively. The OR for RASSF1A methylation in poorly-differentiated vs. moderately/well-differentiated NSCLC tissues was 1.88 (95% CI, 1.32-2.68, P<0.001), whereas there were no significant differences in RASSF1A methylation in relation to gender, pathology, TNM stage and smoking behavior among NSCLC cases. Conclusion: This meta-analysis suggests a significant association between RASSF1A methylation and NSCLC, confirming the role of RASSF1A as a tumor suppressor gene. Large-scale and well-designed case-control studies are needed to validate the associations identified in the present meta-analysis.
RAS associations domain family protein 1A;non-small cell lung cancer;methylation;odds ratio
- Anglim PP, Alonzo TA, Laird-Offringa IA (2008). DNA methylation-based biomarkers for early detection of non-small cell lung cancer: an update. Mol Cancer, 7, 81. https://doi.org/10.1186/1476-4598-7-81
- Baylin SB (2005). DNA methylation and gene silencing in cancer. Nat Clin Pract Oncol, 2, S4-11. https://doi.org/10.1038/ncponc0354
- Brauch H, Johnson B, Hovis J, et al (1987). Molecular analysis of the short arm of chromosome 3 in small-cell and non-smallcell carcinoma of the lung. N Engl J Med, 317, 1109-13. https://doi.org/10.1056/NEJM198710293171803
- Burbee DG, Forgacs E, Zochbauer-Muller S, et al (2001). Epigenetic inactivation of RASSF1A in lung and breast cancers and malignant phenotype suppression. J Natl Cancer Inst, 93, 691-9. https://doi.org/10.1093/jnci/93.9.691
- Chan MW, Chan LW, Tang NL, et al (2003). Frequent hypermethylation of promoter region of RASSF1A in tumor tissues and voided urine of urinary bladder cancer patients. Int J Cancer, 104, 611-6. https://doi.org/10.1002/ijc.10971
- Chen H, Suzuki M, Nakamura Y, et al (2006). Aberrant methylation of RASGRF2 and RASSF1A in human non-small cell lung cancer. Oncol Rep, 15, 1281-5.
- Choi JE, Kim DS, Kim EJ, et al (2008). Aberrant methylation of ADAMTS1 in non-small cell lung cancer. Cancer Genet Cytogenet, 187, 80-4. https://doi.org/10.1016/j.cancergencyto.2008.08.001
- Choi N, Son DS, Song I, et al (2005). RASSF1A is not appropriate as an early detection marker or a prognostic marker for nonsmall cell lung cancer. Int J Cancer, 115, 575-81. https://doi.org/10.1002/ijc.20916
- Dammann R, Li C, Yoon JH, et al (2000). Epigenetic inactivation of a RAS association domain family protein from the lung tumour suppressor locus 3p21.3. Nat Genet, 25, 315-9. https://doi.org/10.1038/77083
- Dammann R, Strunnikova M, Schagdarsurengin U, et al (2005). CpG island methylation and expression of tumour-associated genes in lung carcinoma. Eur J Cancer, 41, 1223-36. https://doi.org/10.1016/j.ejca.2005.02.020
- Guo M, House MG, Hooker C, et al (2004). Promoter hypermethylation of resected bronchial margins: a field defect of changes? Clin Cancer Res, 10, 5131-6. https://doi.org/10.1158/1078-0432.CCR-03-0763
- Agathanggelou A, Cooper WN, Latif F (2005). Role of the Rasassociation domain family 1 tumor suppressor gene in human cancers. Cancer Res, 65, 3497-508. https://doi.org/10.1158/0008-5472.CAN-04-4088
- Akhavan-Niaki H, Samadani AA (2013). DNA Methylation and Cancer Development: Molecular Mechanism. Cell Biochem Biophys.
- Hesson LB, Cooper WN, Latif F (2007). The role of RASSF1A methylation in cancer. Dis Markers, 23, 73-87. https://doi.org/10.1155/2007/291538
- Hsu HS, Chen TP, Hung CH, et al (2007). Characterization of a multiple epigenetic marker panel for lung cancer detection and risk assessment in plasma. Cancer, 110, 2019-26. https://doi.org/10.1002/cncr.23001
- Ito M, Ito G, Kondo M, et al (2005). Frequent inactivation of RASSF1A, BLU, and SEMA3B on 3p21.3 by promoter hypermethylation and allele loss in non-small cell lung cancer. Cancer Lett, 225, 131-9. https://doi.org/10.1016/j.canlet.2004.10.041
- Jemal A, Bray F, Center MM, et al (2011). Global cancer statistics. CA Cancer J Clin, 61, 69-90. https://doi.org/10.3322/caac.20107
- Kang CY, Zhou HC, Tang SP, Xiao H (2011). Values of promoter hypermethylation of FHIT, p 16, MGMT and RASSF 1A genes in plasma in the diagnosis of lung cancer. Tumor, 31, 729-34.
- Kim DS, Cha SI, Lee JH, et al (2007). Aberrant DNA methylation profiles of non-small cell lung cancers in a Korean population. Lung Cancer, 58, 1-6. https://doi.org/10.1016/j.lungcan.2007.04.008
- Kontic M, Stojsic J, Jovanovic D, et al (2012). Aberrant promoter methylation of CDH13 and MGMT genes is associated with clinicopathologic characteristics of primary non-small-cell lung carcinoma. Clin Lung Cancer, 13, 297-303. https://doi.org/10.1016/j.cllc.2011.11.003
- Kwong J, Lo KW, To KF, et al (2002). Promoter hypermethylation of multiple genes in nasopharyngeal carcinoma. Clin Cancer Res, 8, 131-7.
- Li W, Deng J, Jiang P, et al (2012). Methylation of the RASSF1A and RAR(beta) genes as a candidate biomarker for lung cancer. Exp Ther Med, 3, 1067-71.
- Lin Q, Geng J, Ma K, et al (2009). RASSF1A, APC, ESR1, ABCB1 and HOXC9, but not p16INK4A, DAPK1, PTEN and MT1G genes were frequently methylated in the stage I non-small cell lung cancer in China. J Cancer Res Clin Oncol, 135, 1675-84. https://doi.org/10.1007/s00432-009-0614-4
- Liu Z, Zhao J, Chen XF, et al (2008). CpG island methylator phenotype involving tumor suppressor genes located on chromosome 3p in non-small cell lung cancer. Lung Cancer, 62, 15-22. https://doi.org/10.1016/j.lungcan.2008.02.005
- Peng Z, Shan C, Wang H (2010). [Value of promoter methylation of RASSF1A, p16, and DAPK genes in induced sputum in diagnosing lung cancers]. Zhong Nan Da Xue Xue Bao Yi Xue Ban, 35, 247-53.
- Shivakumar L, Minna J, Sakamaki T, Pestell R, White MA (2002). The RASSF1A tumor suppressor blocks cell cycle progression and inhibits cyclin D1 accumulation. Mol Cell Biol, 22, 4309-18. https://doi.org/10.1128/MCB.22.12.4309-4318.2002
- Song H, Yi J, Zhang Y, Wang R, Chen L (2011). DNA methylation of tumor suppressor genes located on chromosome 3p in non-small cell lung cancer. Chin J Lung Cancer, 14, 233-8.
- To KF, Leung WK, Lee TL, et al (2002). Promoter hypermethylation of tumor-related genes in gastric intestinal metaplasia of patients with and without gastric cancer. Int J Cancer, 102, 623-8. https://doi.org/10.1002/ijc.10783
- Toyooka S, Maruyama R, Toyooka KO, et al (2003). Smoke exposure, histologic type and geography-related differences in the methylation profiles of non-small cell lung cancer. Int J Cancer, 103, 153-60. https://doi.org/10.1002/ijc.10787
- Wang J, Lee JJ, Wang L, et al (2004). Value of p16INK4a and RASSF1A promoter hypermethylation in prognosis of patients with resectable non-small cell lung cancer. Clin Cancer Res, 10, 6119-25. https://doi.org/10.1158/1078-0432.CCR-04-0652
- Wang J, Wang B, Chen X, Bi J (2011). The prognostic value of RASSF1A promoter hypermethylation in non-small cell lung carcinoma: a systematic review and meta-analysis. Carcinogenesis, 32, 411-6. https://doi.org/10.1093/carcin/bgq266
- Yanagawa N, Tamura G, Oizumi H, et al (2003). Promoter hypermethylation of tumor suppressor and tumor-related genes in non-small cell lung cancers. Cancer Sci, 94, 589-92. https://doi.org/10.1111/j.1349-7006.2003.tb01487.x
- Yanagawa N, Tamura G, Oizumi H, et al (2007). Promoter hypermethylation of RASSF1A and RUNX3 genes as an independent prognostic prediction marker in surgically resected non-small cell lung cancers. Lung Cancer, 58, 131-8. https://doi.org/10.1016/j.lungcan.2007.05.011
- Yang ZH, Cai YY, Sun LH (2007). Methylation of antioncogen at 3p in non-small cell lung cancer. Chin J Cancer Prev Treat, 14, 363-5.
- Yu MY, Tong JH, Chan PK, et al (2003). Hypermethylation of the tumor suppressor gene RASSFIA and frequent concomitant loss of heterozygosity at 3p21 in cervical cancers. Int J Cancer, 105, 204-9. https://doi.org/10.1002/ijc.11051
- Zhang H, Zhang S, Zhang Z, et al (2010). Prognostic value of methylation status of RASSF1A gene as an independent factor of non-small cell lung cancer. Chin J Lung Cancer, 13, 311-6.
- Zhang Y, Wang R, Song H, et al (2011). Methylation of multiple genes as a candidate biomarker in non-small cell lung cancer. Cancer Lett, 303, 21-8. https://doi.org/10.1016/j.canlet.2010.12.011
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- Aberrant Methylation of RASSF2A in Tumors and Plasma of Patients with Epithelial Ovarian Cancer vol.15, pp.3, 2014, https://doi.org/10.7314/APJCP.2014.15.3.1171
- Association between RASSF1A Ala133Ser Polymorphism and Cancer Susceptibility: A Meta-Analysis Involving 8,892 Subjects vol.15, pp.8, 2014, https://doi.org/10.7314/APJCP.2014.15.8.3691
- Association between Ras association domain family 1A Promoter Methylation and Esophageal Squamous Cell Carcinoma: a Meta-analysis vol.15, pp.9, 2014, https://doi.org/10.7314/APJCP.2014.15.9.3921
- Methylation of RASSF1A gene promoter and the correlation with DNMT1 expression that may contribute to esophageal squamous cell carcinoma vol.13, pp.1, 2015, https://doi.org/10.1186/s12957-015-0557-y
- Types of Cancers Prevailing in Pakistan and their Management Evaluation vol.16, pp.9, 2015, https://doi.org/10.7314/APJCP.2015.16.9.3605
- CpG site-specific RASSF1a hypermethylation is associated with occupational PAH exposure and genomic instability vol.4, pp.4, 2015, https://doi.org/10.1039/C5TX00013K
- Heparanase mRNA and Protein Expression Correlates with Clinicopathologic Features of Gastric Cancer Patients: a Meta-analysis vol.16, pp.18, 2016, https://doi.org/10.7314/APJCP.2015.16.18.8653
- The relationship between RASSF1A gene promoter methylation and the susceptibility and prognosis of melanoma: A meta-analysis and bioinformatics vol.12, pp.2, 2017, https://doi.org/10.1371/journal.pone.0171676