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To Detect The Value Of P16?DAPK And APC Gene Methylation In The Early Diagnosis Of Lung Cancer

Posted on:2019-08-14Degree:MasterType:Thesis
Country:ChinaCandidate:J L LuoFull Text:PDF
GTID:2404330545478092Subject:Cardiothoracic Surgery
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BackgroudAt present,the incidence of lung cancer is ranked first in all countri es in the world.In particular,with the current deterioration of the environ ment and the advancement of urbanization,lung cancer has become the n umber one killer of harm to people's health.Clinically,although lung can cer detection methods are diverse,final diagnosis of lung cancer still requ ires biopsy,and biopsy can also be performed by various methods such a s fiberoptic bronchoscopy,sputum cells,and lung puncture.However,thes e methods of diagnosis are all invasive methods,and it is difficult for so me patients with other complications to perform,and most diagnosed pati ents with lung cancer have entered the late stage or even metastasized.B ecause the symptoms of early lung cancer are not obvious,these complex and invasive diagnostic tools cannot be applied to early lung cancer scre ening.Because of the lack of effective early screening methods,the fiveyear survival rate of lung cancer is low.In western countries with highermedical standards,the five-year survival rate of lung cancer is higher be cause of relatively complete early screening;however,in developing count ries,especially in Africa,the five-year survival rate of lung cancer is eve n less than 5%.Although various inspection techniques have been develop ed and advanced,the diversification and advancement of diagnostic metho ds have made it difficult to further increase the five-year survival rate of lung cancer.And the treatment of lung cancer has made it difficult to ma ke breakthroughs.Therefore,the further exploration of early screening tec hniques for lung cancer is the mission and task of current research and cl inicians.Recently,epigenetics has become a hot topic in current researche s.Epigenetics can participate in the whole development process of tumors from early to late stages.DNA methylation is one of the most important modification methods of epigenetics and has many malignities.DNA met hylation is detected in tumors such as gastric cancer,breast cancer,liver cancer,prostate cancer,bladder cancer,and lung cancer,and these methyla tion mainly occurs in the Cp G island site of the gene promoter region[1].Compared with other sites,the abnormal methylation of CpG islands often leads to transcriptional inactivation of tumor suppressor genes,which in turn leads to the production of tumors.This has been confirmed by s tudying many tumor suppressor genes.Although the mechanism of action of many tumor suppressor genes has been fundamentally studied in the st udy of methylation of lung cancer,the multiple tumor suppressor(MTS)and death-associated protein kinase(DAPK)have been selected comprehen sively in this study.The main reason for the three genes of the adenomat osis polyposis coli(APC)gene is that these three genes have been involv ed in the early stages of lung cancer and play a key role in the relevantpathways.By analyzing the mechanism of methylation of these three gen e promoters in lung cancer,it can provide new effective means for early diagnosis of lung cancer and prediction of lung cancer.Objective:The purpose of this study was to detect the abnormal methylation of p16,DAPK,and APC gene promoters in peripheral blood from patients with lung cancer and to analyze their value in the early diagnosis of lung cancer.Method:1.Research object: A total of 79 patients who were diagnosed as no n-small cell lung cancer by surgery and postoperative pathological examin ation at the First Affiliated Hospital of Guangxi Medical University from October 2016 to August 2017 were selected.All patients had no radiother apy.And chemotherapy and other treatments.At the same time,80 patient s with non-malignant lung cancer who were hospitalized in the Departmen t of Respiratory Medicine at the First Affiliated Hospital of Guangxi Med ical University were selected and were excluded from the history of malig nant tumors in the lungs or other organs.The collection of case data was subject to the subject's consent and support.2.Detection of DNA methylation levels: Real-time fluorescence quanti tative methylation-specific PCR was used to detect the methylation level o f p16,DAPK,and APC gene promoters.3.Experimental data analysis and processing: Analysis software uses SPSS version 17.0.The median and interquartile range are used to descri be data that do not meet the normal distribution.The 2 test was used f or comparative analysis of qualitative data.The Mann-Whitney U test wasused to compare the quantitative data of the skewed distribution between two independent samples.Multivariate unconditional logistic regression w as used to analyze the risk associations of lung cancer with gender,age,smoking,and methylation levels.The receiver operating characteristics(R OC)curve was used to compare the methylation levels of p16,DAPK,an d APC genes in the diagnosis of lung cancer.?=0.05 was used as the tes t level.Results:1.There was no significant difference in age,sex,smoking history b etween lung cancer group and control group(P>0.05);methylation levels of p16,DAPK,and APC genes in lung cancer and control groups were d ifferent.Statistically significant(P<0.05);analysis of methylation rates of p16,DAPK,and APC gene promoters in lung cancer tissues and clinicop athological data(age,gender,smoking,histological type,presence or abse nce of lymph node metastasis,and pathological staging)The association w as not statistically significant(P>0.05).2.According to the percentile method,the promoter methylation level s of p16,DAPK,and APC genes in the lung cancer and control groups were divided into four levels,and unconditional logistic regression analysi s showed that the p16,DAPK,and APC genes were all Risk factors for lung cancer,and as the level of gene methylation increases,the risk of lu ng cancer increases.3.Compare the diagnostic value of detecting single genes and combi ning multiple detection genes for lung cancer.The diagnostic value of ind ividual genes from lung cancer to lung cancer was DAPK(AUC=0.790),p16(AUC=0.787),and APC(AUC=0.746).Compared with single gene detection,the combination of three genes has a higher diagnostic value for l ung cancer,with a marked increase in sensitivity and a decrease in specif icity.Conclusion:1.Methylation of p16,DAPK,and APC gene promoters in peripheral blood is associated with lung cancer.p16,DAPK in lung cancer patients with different ages,sex,and/or history of smoking,different histological types,different pathological stages,and with or without lymph node metas tasis There was no significant difference between the level of APC gene promoter and methylation.2.The p16,DAPK,and APC genes are all risk factors for lung canc er,and as the promoter methylation level increases,the risk of lung canc er increases.3.Combined detection of promoter methylation levels of p16,DAPK,and APC genes has a higher diagnostic value for lung cancer than single detection.Therefore,the use of fluorescent quantitative PCR for the dete ction of promoter methylation levels of p16,DAPK,and APC genes contr ibutes to lung cancer.Early diagnosis.
Keywords/Search Tags:methylation, lung cancer, p16 gene, DAPK gene, APC gene, Quantitative Real-time PCR
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