| Background: Lung cancer is one of the most common malignant tumors in the world.The morbidity and mortality of lung cancer in our country is ranked in the first place among the top four tumors.The reason for such a high mortality rate of lung cancer is due to the lack of early detection methods.The reason of high mortality rate of lung cancer is due to that the vast majority of patients in the clinical recognition of lung cancer has developed to the advanced stage,thus missing valuable treatment period.The 5 year survival rate of lung cancer is less than 15% in the developed areas.It is more and more difficult in our country.Therefore,a sensitive and effective method for early diagnosis of lung cancer is the key to improve the survival rate of patients.With the development of molecular technology,the screening of tumor markers has become a hot spot and focus of researchers.A large number of studies have shown that the abnormal expression of tumor suppressor genes in the early stage of carcinogenesis may result in the silencing of tumor suppressor genes.Therefore,the aberrant methylation of the promoter region of tumor suppressor genes may be effective markers for lung cancer early detection.Objective: 1)To investigate the relationship between aberrant methylation of promoter region of RUNX3,RASSFlA and DAPK,and the susceptibility to lung cancer.2)To investigate the abnormal methylation status of RUNX3,RASSF1 A,3-OST-2,DAPK,PTPRO promoter and the value of combined detection for the early diagnosis of lung cancer.Methods: 1)To study the relationship between methylation of RUNX3,RASSFlA and DAPK genes,with susceptibility to lung cancer,a Meta-analysis was carried out.First,literatures related to lung cancer RUNX3,RASSF1 A,and DAPK methylation were collected from PubMed,EMBASE,Ovid,Web of science,CBM,VIP,CNKI,wanfang database.Second,the literatures were screened according to the inclusion and exclusion criteria;Finally,RevMan5.2 software was used for statistical analysis.2)91 plasma samples were collected from Hebei University Affiliated Hospital and Baoding First Central Hospital from March 2015 to August 2016.All patients were diagnosed with primary lung cancer and confirmed by pathological or cytological diagnosis.Plasma samples were collected before surgery and chemotherapy.58 cases of healthy blood samples were also collected as the control group.Methylation specific PCR(methylation specific-PCR,MSP)was used to detect gene methylation.Results: 1)The results of meta-analysis showed:(1)A total of 36 articles were included in the study,RUNX3 gene was included in 10,RASSF1 A gene in 20,DAPK gene in 13.(2)The RUNX3 gene methylation rate in patient group was significantly higher than the control group(35.22%>9.2%,OR=5.89,95%CI:4.17~8.32,P<0.05);a subgroup analysis showed that methylation of RUNX3 gene in lung cancer tissues were significantly higher than that in normal tissues(OR=4.59,95%CI:3.20~6.59,P<0.05)and blood compared with statistical significance(OR=63.24,95%CI:8.54~468.37,P<0.05).(3)the methylation of RASSF1 A gene in case group was 41.30%,the control group was 2.31%,with statistic value of OR was 23.91(95%CI:16.55~34.54,P<0.05),further to the methylation of this gene in tumor tissue and blood in sputum were analyzed,the methylation rate of tissues(OR=21.13,95%CI:13.64~32.74,P<0.05)with similar blood methylation rate(OR=83.96,95%CI:26.29~268.08,P<0.05),the methylation rate was higher than the rate of methylation in sputum(OR=8.28,95%CI:3.18~21.59,P<0.05).(4)the DAPK gene methylation rate in the patient group was 42.11% higher than the methylation rate of 7.16% in the control group(OR=9.98,95%CI:5.91~16.87,P<0.05),sub group showed that the gene methylation in tumor tissues(OR=8.83,95%CI:5.10~15.29,P<0.05 rate)is higher than that of blood samples(OR=39.32,95%CI:7.68~201.26,P<0.05).2)The plasma of patients with NSCLC RUNX3,RASSF1 A,3-OST-2,DAPK,PTPRO gene methylation rate were 47.25%(43/91),51.65%(47/91),27.47%(25/91),36.26%(33/91),41.76%(38/91),respectively;while in the control group,only PTPRO gene methylation was detected in the and the methylation rate was 5.2%(3/58),and the rest of RUNX3,RASSF1 A,3-OST-2 and DAPK genes were not detected methylation.There was significant statistical difference between the experimental group and the control group(P < 0.05).The methylation of RUNX3 gene was associated with the type of lung cancer and the degree of tissue differentiation(P < 0.05);the methylation of RASSF1 A gene was higher than that of high differentiation(P < 0.05);The methylation of DAPK gene was associated with the clinical stage of lung cancer,and the methylation rate in stage III and IV was higher than that in stage I and II(P < 0.05);There was no significant difference between 3-OST-2 gene and PTPRO gene methylation and clinical pathological features(P > 0.05).The methylation of 5 genes was detected and the sensitivity was increased to 92.31%(84/91)and the specificity was 94.83%.Conclusion: 1)The result of meta-analysis showed that RUNX3,RASSF1 A and DAPK gene methylation were closely related to lung cancer susceptibility.2)The methylation of rate RUNX3,RASSF1 A,3-OST-2,DAPK,PTPRO genes were significantly higher in lung cancer patient plasma than in normal plasma;the methylation rate of combined detection of plasma levels of the 5 genes is higher than the detection rate of methylation of any single gene,indicating that combination of detecting methylation genes is more accurate in the early diagnosis of lung cancer. |
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