Methylation Of RASSF1A And CDH13Genes In Individualized Chemotherapy For Patients With Non-small Cell Lung Cancer

Lung cancer is one of the malignant tumors which has the highest morbidity andmortality in the world. The majority of that patients with non-small cell lungcancer(NSCLC) would not even find out the situation until the cancer has reached itslate stage,lost the chance of operation.So the chemotherapy is still the important methodfor the treatment of advanced non small cell lung cancer patients.However, due todifference of chemotherapy sensitivity between different patients, the effect ofchemotherapy is not ideal,even lead to the progression of disease.Therefore, in order toprolong the survival time of patients with NSCLC,to improve the quality of life of thesepatients,the application of individualized chemotherapy is particularlyimportant.Because of the methylation of promoter region is a reversibleprocess,detection of gene methylation levels may provide guidance for theindividualized chemotherapy.It has been suggested that methylation of RASSF1A andCDH13genes promoter region is closely related to the occurrence of NSCLC.As tumorsuppressor gene,RASSF1Aand CDH13genes methylation occur frequently in NSCLC.Objective:This study aimed to investigate the correlation between methylation of RASSF1Aand CDH13genes promoter region to the genesis and progress of NSCLC．Evaluate themethylation of RASSF1A and CDH13genes promoter region as a marker formonitoring chemotherapeutic efficacy in personalized medicine for patients with NSCLC,provide a new direction for NSCLC individualized chemotherapy.Methods:42NSCLC patients and40healthy controls were included.Collected the patients’blood in the whole process of chemotherapy.The methylation of RASSF1A and CDH13genes promoter region were detected by the method of methylation specific polymerasechain reaction (MSP).Compared the methylation rate of RASSF1A and CDH13genespromoter region between the patients and the healthy controls.According to the effect ofchemotherapy,patients were divided into partial remission(PR) group,stable disease(SD)group and progressive disease(PD) group.Compared the methylation of RASSF1A andCDH13genes promoter region between eath two groups,moreover,Compared with thehealthy control group.Results:1.The rate of RASSF1A and CDH13genes methylation in42cases of NSCLCpatients is significant higher than in40cases of healthy controls(52.4%to0.0%,54.8%to0.0%,P<0.05).2.Hyper-methylation of RASSF1A and CDH13genes was not associated withgender,age,smoking,pathological type and TNM staging system．3.After the chemotherapy,the hyper-methylation of RASSF1A and CDH13genes inPR group and SD group decreased significantly(P<0.05),and were significantlydifferent from which in PD group(P<0.05),but had no statistical different comparedwith that in healthy controls(P>0.05).4.In42cases of NSCLC patients,the methylation rate of RASSF1A gene before thefirst time of chemotherapy,after the second time of chemotherapy,after the fourth timeof chemotherapy,after the sixth time of chemotherapy was52.4%,45.2%,33.3%,26.2%.It showed a gradual downward trend.Meanwhile,the methylation rate of CDH13gene was54.8%,38.1%,31.0%,26.2%,showed a gradual downward trend.Conclusion:1.The methylation of RASSF1A and CDH13genes between NSCLC patients andhealthy controls is significantly different.There is a higher rate of RASSF1A and CDH13genes methylation in NSCLC.It means that the methylation of RASSF1A andCDH13genes occur more frequently in NSCLC patients.2.The RASSF1A and CDH13genes methylation level have no correlation togender,age,smoking status,pathological type and TNM stage.3.The methylation rate of RASSF1A and CDH13genes decreased in the course ofchemotherapy,the change associated with the effect of chemotherapy.The methylationlevel return to normal in the patients who have higher sensitivity to chemotherapeutic.