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The Expression And The Clinical Significance Of Autophagy-related Genes Beclin1 And PTEN In Thyroid Carcinoma

Posted on:2012-01-02Degree:MasterType:Thesis
Country:ChinaCandidate:Y H ZhangFull Text:PDF
GTID:2154330332996317Subject:Immunology
Abstract/Summary:PDF Full Text Request
Background:Recently the incidence of thyroid carcinoma rises every year all over the world, with its annual growth of about 4%, which has attracted particular attention to most people. Meanwhile, TC has become one of the hottest research fields in endocrine system. Over the past years, conventional chemoradiation has been used for the treatment of ineffective thyroid carcinoma with the traditional treatment method of "Surgery+Iodine 131+Thyroxin". But its effect appears quite limited, including the single or combined chemotherapy in the treatment of refractory thyroid cancer with the Adriamycin approved by the U.S. FDA. However, with the appearance of Molecular targeted therapy for TC, it has brought some changes to the treatment model for refractory thyroid carcinoma.Autophagy is called TypeⅡapotosis, which is the important mechanism for the cells adapting to the environment changes and defending the pathogenic microorganisms from invading. Moreover, it can maintain homeostasis and maintain the health of humans and other eukaryotes. More and more studies have shown that changes in autophagic activity in a variety of human tumor cells exist.Beclinl gene also can be called BECN1 gene, it is the double alleles tumor-suppressor gene which the mammals use in autophagy. It is located on human chromosome 17q21, and the loss of heterozygosity is one of the reasons for the cells' deterioration and transformation. It has shown that it plays an important role in the occurrence and development of cancer by participating in the autophagy body's formation and autophagy levels' regulation.Till now PTEN is the first but also the most frequently mutated cancer suppressor gene with double specific phosphatase activites, which is located on human chromosome 10q23.3. PTEN can inhibit PI3K/PKB pathway and make the cell autophagy open so that it can promote the formation of autophagy and inhibit the development of tumor.In many researches, it is suggested that both the Beclinl and PTEN can be involved in the regulation of autophagic activity in malignant cells. By now there are few reports about the expression of autophagy protein level in TC, and the protein expression about PTEN in thyroid cancer has been reported rarely. Regarding to the regulation of thyroid cancer cells's autophagy activity with both the Beclinl and PTEN are not mentioned before.Objects:In this present study, the writer not only examined both the Beclinl and PTEN's expression in the thyroid cancer, the benign thyroid and the normal thyroid tissue, but also analyzed the correlation between each other. Besides, its effects and relationships during the occurrence and development of thyroid cancer were introduced. The writer also made an analysis of thyroid cancer tissue Beclinl and PTEN's expression and relevancy of clinical parameters, such as clinical stages, tissue type, and grade of cell differentiation, lymph node metastasis, and capsular infiltration and so on. Finally, the writer revealed the clinical significance of Beclinl and PTEN in the thyroid cancer. It is hoped that this research can provide the basis for the search of the effective therapeutic target and for the new therapeutic approaches.Method:1.The writer selected pathology archived paraffin specimens from 2008 January to 2010 June in Xinzhou City People's Hospital, in which all together 113 people are chosen,79 subjects with thyroid cancer and another 34 with benign thyroid. At the same time,15 people were picked out with surgical resection of thyroid tissue over the same period for comparison.2.The writer recorded the tumor size, tissue type, clinical stage, lymph node metastasis, capsular infiltration and other clinical parameters of each subject. One point should be stressed is that all subjects did not do any chemotherapy and radiotherapy before the surgery.3.Both the protein expression of Belinl and PTEN in thyroid cancer, benign thyroid and normal thyroid tissue were analyzed by Immunohistochemistry Method. And the correlation analysis with clinicapathological parameters was carried out.4.All the data was analyzed with the SPAA 13.0 packages.Result:1.Expression of Beclinl protein:Beclinl espression fell off from normal thyroid organization, thyroid benign lesionsto thyroid cancer tissue,(χ2=13.67, p=0.001).Beclinl negative rate was significantly lower in normal thyroid organization(80.00%) than in thyroid benign lesions(58.82%) and thyroid cancer tissue(34.18%),respectively.2.Relationship between Beclinl and cliicopathologic:Beclinl expression was associated with the lymphnode metastasis(χ2=7.202, p=0.007),but with age, gender differentiation degree, tumor size,pathologic, coated infringe(χ2=0.084, p=0.773;χ2=0.046, p=0.831;χ2=0.402, p=0.940;χ2=1.241, p=0.265;χ2=0.018, p=0.894;χ2=2.011, p=0.156).3.Expression of PTEN protein:PTEN espression fell off from normal thyroid organization, thyroid benign lesionsto thyroid cancer tissue,(χ2=31.75, p=0.000).PTEN negative rate was significantly lower in normal thyroid organization(86.67%) than in thyroid benign lesions(64.71%) and thyroid cancer tissue(32.91%),respectively.4.Relationship between pten and cliicopathologic:PTEN espression was associated with the lymphnode metastasis(χ2=15.39, p=0.000)and differentiation degree (χ2=5.462, p=0.012), but with age,gender,umor size,pathologic, coated infringe(χ2=0.342, p=0.555;χ2=0.012, p=0.914; χ2=1.247, p=0.742;χ2=0.200, p=0.655;χ2=0.059, p=0.808).5. Correlation between Beclinl and PTEN:Beclinl espression has a postive corrlation with PTEN in 79 specimens of thyroid cancer(rs=0.5929, p=0.000).Conclusion1.From the normal thyroid tissue, benign thyroid lesions to thyroid cancer, the protein expression of Belinl and PTEN gradually decreases, which suggests that autophagy-related genes Beclinl and PTEN may play a role in the occurrence and development of thyroid cancer.2.As shown, the positive rate of Beclinl protein has something to do with the lymph node metastatsis, which suggests that autophagy activity decline may have certain relation with the prognosis of thyroid cancer.3.The positive rate of PTEN protein is relevant to clinical stage, lymph node metastatsis, which suggests that PTEN expression protein progressively decreases with the increasing degree of malignancy during the development of thyroid cancer. It can be taken as the potential marker to show the degree of malignancy of thyroid cancer.4.The relativity of the Belinl and PTEN protein is quite good, which hints that the Belinl and PTEN may interact with each other and jointly participate in the thyroid cancer and development of papillary thyroid cancer.
Keywords/Search Tags:autophagy, Beclinl, PTEN, thyroid carcinoma, immunohistochemistry
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