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The Characteristics Of PIK3CA Gene Mutations In Breast Cancer With And Without Diabetes Mellitus

Posted on:2016-11-16Degree:MasterType:Thesis
Country:ChinaCandidate:P F YuanFull Text:PDF
GTID:2284330479451372Subject:Surgery
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Breast cancer is one of the most common cancer in women. Its incidence is increasing year by year, which seriousely threatened the physical and mental health of women. Epidemiological studies suggest that breast cancer and diabetes mellitus(DM) often exist at the same time, and the risk of breast cancer in the women with DM is higher than those without DM, especially in postmenopausal women. Many research results show that there is a significant correlation between breast cancer and DM at home or abroad.The carcinogenesis and progression of breast cancer are a multiple factor and stage of complex process, in which it plays important role that the activation of protooncogenes and deactivation of tumor-suppressor genes lead to the abnormal proliferation of cells. Phosphatidyl inositol-3 kinase(PI3K) is one kind of lipid kinase, which can be divided into three type depending on its structures, including Class type I, Class type II and Class type III. Type I PI3 K is a dimer composed of catalytic subunit p110 and regulating subunit p85. PI3 K plays an important role in cell proliferation, apoptosis and tumor formation. The α subunits of phosphoinositide 3-kinase(PIK3CA) encodes Class I PI3 K catalytic subunit P110 alpha. PIK3 CA has been a oncogene, which has been found there are high-frequency mutations in many tumors,and its mutation causes the activation of PIK3/Akt signaling pathway and is related to the incidence of breast cancer, ovarian cancer, non-small cell lung cancer, liver cancer, gastric cancer, and colorectal cancer. According to the reports in literature, there exists high-frequency mutations of PIK3 CA in breast cancer, but whether there was the relationship between it and clinicopathological feature of breast cancer was not determined. There was no report about the characteristics of PIK3 CA gene mutations in breast cancer with DM at home and abroad. Thus, we design this experiment to explore the characteristics of PIK3 CA gene mutation in breast cancer with and without DM, for providing theoretical basis for the pathogenesis, early diagnosis and individualized treatment of breast cancer.Objective: To study the characteristics of PIK3 CA gene mutations in breast cancer with DM, and analyze its relationship with clinicopathological feature of breast cancer patients, for exploring the role of PIK3 CA gene in the carcinogenesis and development of breast cancer and its clinical significance.Methods: 100 cases of breast cancer patients were selected and patients’ carcinoma tissue samples were collected from the First Affiliated Hospital of Henan University of Science and Technology, including 50 cases of breast cancer with DM and 50 cases breast cancer without DM. Another 20 samples of benign breast tumor were chosen as control group. After extracting different tumor DNA from samples of breast cancer, ultraviolet spectrophoto-metry was used to detect the concentration and purity, PCR technology was used to amplify exons 9 and 20 of the tumor DNA, and after purifying the product, DNA sequence were tested. The characteristics of PIK3 CA gene mutations in tumor tissue of every groups and their relationships with clinical pathological features in breast cancer were analyzed.Results:1.PIK3 CA mutation was not found in 20 cases of benign breast tumor. The mutation were observed in 18(36%) of the group of 50 cases of breast cancer without DM, and 7(39%) occurred in exon 9 and 11(61%) in exon 20. The mutation were observed in 4(8%) of the group of 50 cases of breast cancer with DM, and 1(25%) occurred in exon 9 and 3(75%) in exon 20.2. There was no significant correlation between PIK3 CA gene mutation and age, tumor size, lymph node status, histological type, clinical stages, differentiation of tumor, and HER-2 expression(P>0.05), but it was associated with ER and PR expression(P<0.05).Conclusion:1.Mutation frequency of PIK3 CA gene found in breast cancer without DM group is higher than with DM group. PIK3 CA gene may be related to the carcinogenesis and development of breast cancer without DM, but the experimental evidence does not confirmed PIK3 CA gene mutation does not involved in the development of breast cancer with DM. Its molecular mechanism needs further research.2.The mutations of PIK3 CA gene were associated with ER and PR expression which influence the prognosis of patients with breast cancer. It can be inferred that PIK3 CA gene may be involved in the change of breast cancer biological behavior, which can provide a reference value for the prevention and treatment of breast cancer.
Keywords/Search Tags:Breast cancer, Diabetes mellitus, PIK3CA gene, Gene mutation
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