Gene Expression Profiles of K-ras Activated Mutation in Non-Small Cell Lung Cancer

• Main Authors: Cheng-Yuan Wang, 王程遠
• Other Authors: 黃明賢
• Format: Others
• Language: zh-TW
• Published: 2006
• Online Access: http://ndltd.ncl.edu.tw/handle/48775143523841920001

碩士 === 高雄醫學大學 === 醫學研究所碩士班 === 94 === The biomarkers of lung cancer that can significantly affect the prognosis of the patients and the effectiveness of anti-cancer drug therapy are (1) K-ras mutation (2) EGFR mutation (3) biomarkers of neuroendocrine features. From literature review, we know that the prevalence of lung cancer is increasing, the prevalence of smoking is increasing too, and K-ras mutation is significantly correlated with the smoking status. So the role of K-ras mutation is lung cancer carcinogenesis is becoming more and more significant. Our study focused on the feasibility of predicting K-ras mutational status by analyzing the gene expression profile of peripheral blood by membrane array, and the roles of K-ras mutation in lung cancer carcinogenesis. We sieve out 28 genes that most related to the mutated K-ras associated carcinogenetic pathway by means of comparative genome hybridization and bioinformatics. Then we constructed the membrane array including these 28 genes. We collected 30 coupled lung cancer tumor tissue and peripheral blood samples. By direct sequencing of the tumor tissue, the K-ras mutation rate is 36.7% (11/30), the hot spots of K-ras mutation are codon 12 (81.9%) and codon 13 (18.1%). There are 11 patients have positive results on membrane array on peripheral blood analysis, compared with the results of tumor tissue direct sequencing, the sensitivity, specificity and accuracy of the membrane array are 81.8%, 89.5%, 86.7% respectively. The kappa statistic is 0.713, revealed a good correlation between membrane array and direct sequencing. The K-ras mutation rate of the male and the female are 21.4% and 50% respectively. The K-ras mutation rate in early stage(stage I+II) and late stage lung cancer(stage III+IV) are 21.4% and 50% respectively. The membrane array positive rate of the male and female are 21.4% and 50% respectively, the membrane array positive rate in early stage and late stage lung cancer are 28.6% and 43.8% respectively. The K-ras mutation rate and membrane array positive rate is higher in women and in late stage lung cancer, but not statistically significant. TBX19 is over-expressed more commonly in late stage lung cancer (43.8%) than in early stage lung cancer (7.1%), and is statistically significant (p<0.05). Besides, we find out 4 genes that their over-expression is significantly correlated with K-ras mutation. These four genes include BCL2 (p<0.001), E2F4 (p<0.001), MMP1 (p<0.05), TBX19 (p<0.001). The next step of our study is to clarify the relationship between the four genes and the mutated K-ras in lung cancer carcinogenesis.