Methylation of the RASSF1A and RARβ genes as a candidate biomarker for lung cancer

Abstract

Abstract. Promoter methylation of the RASSF1A and RARβ genes has been associated with susceptibility to different types of cancer. In addition, RASSF1A and RARβ methylation plays an important role in the pathogenesis of lung cancer. We investigated the aberrant promoter methylation of RASSF1A and RARβ in lung cancer patients using methylation-specific polymerase chain reaction (MSP). Aberrant promoter methylation of the RASSF1A gene was detected in 45 of 56 (80.36%) cancer patients and aberrant promoter methylation of the RARβ gene was found in 48 of 56 (85.71%) cases; promoter methylation of both genes was found in 42 of 56 (75%) lung cancer cases. None of the 52 samples from controls exhibited DNA methylation in these two target genes. Methylation was significantly associated with the lung cancer cases compared to controls for the RASSF1A gene (adjusted OR=7.50; 95% CI, 3.935-14.296; p<0.001); similar results were obtained for methylation of the RARβ gene (adjusted OR=5.727; 95% CI, 3.348-9.797; p<0.001). In addition, the association remained significant in these two target genes (adjusted OR=8.429; 95% CI, 4.205-16.896; p<0.001). Our results indicated that the high percentage of promoter methylation in the RARβ and RASSF1A genes indicate their important role in the development of lung cancer in the population studied, and that risk of lung cancer for carriers positive for both genes is higher than in single-gene positive carriers, which may serve as a useful marker for prognosis and a target for the treatment of lung cancer.

Associations Between RASSF1A Promoter Methylation and NSCLC: A Meta-analysis of Published Data

“…The OR in the autologous control subgroup was 17.69 (95%CI, 12.51-25.02; P < 0.001) and the OR in the heterogeneous control subgroup was 32.43 (95%CI, 12.44-84.53; P < 0.001) (Figure 2). In the subgroup analysis of ethnicity, the OR for the Caucasian subgroup was 26.55 (95% CI, 10.86-64.88; P < 0.001) from 4 studies Guo et al, 2004;Wang et al, 2004;Dammann et al, 2005), for the Asian subgroup was 20.94 (95% CI, 14.41-30.43; P <0.001) from 14 studies Ito et al, 2005;Chen et al, 2006;Hsu et al, 2007;Kim et al, 2007;Yanagawa et al, 2007;Yang et al, 2007;Liu et al, 2008;Lin et al, 2009;Peng et al, 2010;Zhang et al, 2010;Kang et al, 2011;Song et al, 2011;Li et al, 2012) (Figure 2).…”

“…Moreover, one was excluded as a duplicate publication . Ultimately, 19 publications met the inclusion criteria (Figure 1) Toyooka et al, 2003;Guo et al, 2004;Wang et al, 2004;Choi et al, 2005;Dammann et al, 2005;Ito et al, 2005;Chen et al, 2006;Hsu et al, 2007;Kim et al, 2007;Yanagawa et al, 2007;Yang et al, 2007;Liu et al, 2008;Lin et al, 2009;Peng et al, 2010;Zhang et al, 2010;Kang et al, 2011;Song et al, 2011;Li et al, 2012) and were included in the meta-analysis. Detailed characteristics of the 19 studies are listed in Table 1.…”

“…Detailed characteristics of the 19 studies are listed in Table 1. Overall, 5 of the included articles were published in Chinese Peng et al, 2010;Zhang et al, 2010;Kang et al, 2011;Song et al, 2011), and the others were published in English Toyooka et al, 2003;Guo et al, 2004;Wang et al, 2004;Choi et al, 2005;Dammann et al, 2005;Ito et al, 2005;Chen et al, 2006;Hsu et al, 2007;Yanagawa et al, 2007;Liu et al, 2008;Li et al, 2012). The aforementioned 19 studies provided data regarding RASSF1A promoter methylation in 2063 cases of NSCLC tissues and 1184 controls of non-tumor tissues, with a total sample size of 3247 cases.…”

“…14 studies calculated the OR of RASSF1A promoter methylation in NSCLC cases and autogenous controls Toyooka et al, 2003;Guo et al, 2004;Wang et al, 2004;Choi et al, 2005;Ito et al, 2005;Chen et al, 2006;Hsu et al, 2007;Kim et al, 2007;Yanagawa et al, 2007;Yang et al, 2007;Liu et al, 2008;Song et al, 2011), and the other 5 studies involved heterogeneous tissue as controls Peng et al, 2010;Zhang et al, 2010;Kang et al, 2011;Li et al, 2012). The OR in the autologous control subgroup was 17.69 (95%CI, 12.51-25.02; P < 0.001) and the OR in the heterogeneous control subgroup was 32.43 (95%CI, 12.44-84.53; P < 0.001) (Figure 2).…”

Combined Effects Methylation of FHIT, RASSF1A and RARβ Genes on Non-Small Cell Lung Cancer in the Chinese Population

“…The Ras association domain family 1 A (RASSF1A) gene located on chromosome 3 at band p21.3 (3p21.3) (Neyaz et al, 2008;Liu et al, 2013;Vo et al, 2013), and retinoic acid receptor beta (RARβ) is to the p24 band of chromosome 3 (Virmani et al, 2000;Li et al, 2012). Aberrant methylation of FHIT, RASSF1A and RARβ were reported separately in lung cancer.…”