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The Association Analysis Between Driver Gene Mutations Of EGFRKRASEML4-ALK And Clinical Features Of Patients Of Lung Cancer

Posted on:2016-07-23Degree:DoctorType:Dissertation
Country:ChinaCandidate:X B JiaFull Text:PDF
GTID:1314330512952635Subject:Surgery
Abstract/Summary:PDF Full Text Request
Driver genes of lung cancer play important roles in lung cancer development and target therapy. The current target reagents TKIs target to EGFR mutations and get better effect. So detection of the driver genes mutation is very important to target therapy of lung cancer. To investigate the association between EGFR, KRAS and EML4-ALK and clinical characters, 1116 patients diagnosis by pathological diagnosis were enrolled and their detail clinical information were collected. ARMS technology was used to genotype the mutations of EGFR, KRAS and EML4-ALK.The results showed that the mutation rate of EGFR is 52.2% in East China, and the rate of 19-del is 19.2%, the rate of L858 R is 24.4%. The mutation rate of KRAS and EML4-ALK is about 5%. Base on the histological classification, the non-small cell lung cancer is 94.1%, including 73.3% adenocarcinoma, 17.8% squamous carcinoma, 3% large cell carcinoma. The mutation rate of small cell lung cancer is1.4%. More female were found in adenocarcinoma, and more male were found in squamous carcinoma, large cell carcinoma and small cell lung cancer. GGO were found in adenocarcinoma, and solid tumor was mostly found in squamous carcinoma,large cell carcinoma and small cell lung cancer. In smoking analysis, we found that smoking status is significantly associated with different kinds of lung cancer, more in squamous carcinoma, large cell carcinoma and small cell lung cancer, but less in adenocarcinoma. The mutation frequency of driver genes were found more higher in adenocarcinoma(61.8%), but lower mutation of KRAS and EML4-ALK(5.7% and 6%,respectively). EGFR mutation was less in squamous carcinoma, large cell carcinoma and small cell lung cancer.In the association analysis, EGFR mutation is more common in female compared with male, OR=2.494,95%CI=1.857-3.351,P<0.001;and more in older which larger than 60 year old, OR=1.300,95%CI=1.002-1.688,P=0.049. The mutation rate of EGFR is significantly decreased in non-smoking Patients, OR=0.583,95%CI=0.430-0.790,P=0.001, and the mutation rate was decreased as the smoking amount decreased, OR=0.606,95%CI=0.470-0.780,P for trend is less than 0.001.The trend of 19-del and L858 R is similar with EGFR. We also found KRAS mutations were significantly associated with smoking. In contrast with EGFR, the mutation rate is more higher in smoking patients, OR=2.469,95%CI=1.232-4.949,P=0.011, and the mutation rate was increased as the smoking amount increased, OR=1.872,95%CI=1.156-3.032,P=0.011.We further analyzed the association between driver gene mutation and subtypes of lung cancer which was classified based on IASLC/ATS/ERS. The lung cancer was divided into three subtypes, Pre-invasive lesions, minimally invasive adenocarcinoma,and invasive adenocarcinoma. The results showed that the mutation rate of EGFR was significantly associated with the degree of invasion, the mutation rate was highest in invasive adenocarcinoma, and lowest in pre-invasive lesions, the moderate in minimally invasive adenocarcinoma, OR=2.269,95%CI=1.595-3.229,P for trend was less than 0.001. The results were similar to 19-del and L858 R. In invasion adenocarcinoma, we also found the mutation rate of EGFR was significantly associated with invasion, OR=1.795,95%CI=1.522-2.118,P for trend was less than0.001。19-del and L858 R had the similar results, OR=1.621,95%CI=1.327-1.981,P<0.001(19-del) and OR=1.899,95%CI=1.557-2.316,P<0.001(L858R).\This study was carried out to investigate the association between driven gene mutation and clinical features, and had comprehensive understanding about EGFR,KRAS and EML4-ALK mutation and clinical features. This would be helpful to clinical thera Py of lung cancer.
Keywords/Search Tags:lung cancer, EGFR, KRAS, EML4-ALK, association analysis
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