Methylation Patterns Of Epidermal Growth Factor Receptor Gene Promoter In Lung Cancer

BackgroundLung cancer has the highest mortality rate in the world at present. In China,it is the leading cause of death of malignant tumor patients, accounting for22.7%of all cancer death, and the incidence and mortality are still rising fast. Mostpatients are already at advanced stage when they are diagnosed, and more than50%of these patients are advanced non-small-cell lung cancer. Most patientsneed chemotherapy because they have lost the operation chance. The first-linechemotherapy of lung cancer is tow drugs combination regimen includingplatinum. The epidermal growth factor receptor kinase inhibitors(EGFR-TKI)play an important role in molecular target therapy of lung cancer. The highexpression of EGFR is the basis of the application of EGFR-TKI. The deletionmutation in exon19and point mutation in exon21are closely related with drugefficacy. A proportion of lung cancer patients with EGFR Mut＋displayacquired resistance to EGFR-TKI. Mechanism of drug resistance ofnon-small-cell lung cancer to EGFR-TKI is still not entirely clear. With the further research of epigenetics, researchers have found out that there is a closerelationship between DNA methylation and malignant tumors. DNA methylationat gene promoter CGIs leads to silencing of tumor suppressor gene and oncogene.It cannot change the sequence of DNA and is reversible, so DNA methylationmay become a new target of tumor treatment. EGFR has a large CpG island thatextend into exon1. EGFR gene display a high CpG methylation state in somesolid tumor patients and this oncogene has a lower expression，even noexpression.PurposesThe aim of this study is to detect the EGFR gene methylation state anddiscuss the relationship between the clinical characteristics, EGFR mutation,andthe EGFR methylation of lung cancer, providing a theory basis for target therapyfor lung cancer.ContentWe collected the lung cancer tissue samples in non-small cell cancers andextract the genomic DNA with the TIANamp Genomic DNA Kit and themethylation status of EGFR gene promoter was determined by bisulfite treatment.DNA with methylated CmpG at the nucleotide position5was processed using theEZ DNA Methylation-Gold Kit. The methylated DNA was amplified by PCR andthen sequenced directly. We investigated the pathological characteristics of thesepatients that had been stratified according to methylation status. The result wascompared using the chi-square test and Fisher Exact test.ResultsIn the first part of our research, we found out that the EGFR promotermethylation was observed in23of76NSCLC samples that were examined. Themethylation rate is30.3%. The methylation state of patients with lung cancer has no significant correlation with gender, age, smoking history, lymph nodemetastasis, infiltrating degree and TNM stage and is related to the pathologicaltype. In the second part of this research, we could see that the EGFR methylationis related to the mutation type of exon19、21.ConclusionEGFR gene promoter methylation in NSCLC patients has a high detectionrate and it may be related to lung cancer. These is a significant associationbetween EGFR promoter methylation and the athological type and the mutationtype of exon19、21.