Abstract
Epigenetic modifications of tumour suppressor genes are involved in all kinds of human cancer. Aberrant promoter methylation is also considered to play an essential role in development of lung cancer, but the pathogenesis remains unclear.We collected the data of 112 subjects, including 56 diagnosed patients with lung cancer and 56 controls without cancer. Methylation of the FHIT, RASSF1A and RAR-β genes in DNA from all samples and the corresponding gene methylation status were assessed using the methylation-specific polymerase chain reaction (PCR, MSP). The results showed that the total frequency of separate gene methylation was significantly higher in lung cancer compared with controls (33.9-85.7 vs 0 %) (p<0.01).Similar outcomes were obtained from the aberrant methylation of combinations of any two or three genes (p<0.01). There was a tendency that the frequency of combinations of any two or three genes was higher in stage I+II than that in stage III+IV with lung cancer. However, no significant difference was found across various clinical stages and clinic pathological gradings of lung cancer (p>0.05).These observations suggest that there is a significant association of promoter methylation of individual genes with lung cancer risk, and that aberrant methylation of combination of any two or three genes may be associated with clinical stage in lung cancer patients and involved in the initiation of lung cancer tumorigenesis. Methylation of FHIT, RASSF1A and RARβ genes may be related to progression of lung oncogenesis.
Highlights
Lung cancer is the most common malignant tumor originating and the most common cause of death from cancer (Missaoui et al, 2010), and increasing numbers of individuals suffer from the disease every year
No significant difference was found across various clinical stages and clinic pathological gradings of lung cancer (p>0.05).These observations suggest that there is a significant association of promoter methylation of individual genes with lung cancer risk, and that aberrant methylation of combination of any two or three genes may be associated with clinical stage in lung cancer patients and involved in the initiation of lung cancer tumorigenesis
Aberrant methylation of FHIT, RASSF1A and RARβ were reported separately in lung cancer. These findings suggest that FHIT, RASSF1A and RARβ are a putative tumor suppressor gene and are likely to be involved in the genesis of lung cancer, which plays an important role in the pathogenesis and progression of lung cancer
Summary
Lung cancer is the most common malignant tumor originating and the most common cause of death from cancer (Missaoui et al, 2010), and increasing numbers of individuals suffer from the disease every year. Lung cancer was found to be the first highest malignant disease in Chinese population in 2007 (Jemal et al, 2009; Missaoui et al, 2010; Bodoor et al, 2014). The prognosis of non-small cell lung cancer (NSCLC) patients remains poor because that no curative treatments are available, in despite of multimodal therapies including surgery, radiotherapy, and chemotherapy (Toyooka et al, 2004; Jemal et al, 2009; Bodoor et al, 2014). DNA methylation of CpG sites in the promoter regions or the first exon of genes is a frequent epigenetic event in cancers of the breast, liver, lung and others (Botana-Rial et al, 2012; Fujiwara et al, 2012).
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