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The Mechanism Of Periostin In Thyroid Carcinoma And The Study Of Lymph Node Metastasis In Papillary Thyroid Microcarcinoma

Posted on:2018-10-12Degree:DoctorType:Dissertation
Country:ChinaCandidate:M WangFull Text:PDF
GTID:1484305156989339Subject:General surgery
Abstract/Summary:PDF Full Text Request
Thyroid cancer is the most common endocrine malignancy.Since the 1990s,the incidence of thyroid cancer has grown rapidly,and its growth rate is the fastest in all malignancies of the same period.Moreover,the rapid growth is real,and it is not generally believed that it is only due to over-diagnosis.At present,thyroid cancer has become the fifth highest incidence of malignant tumor in women.Although the mortality rate of thyroid cancer is relatively low(0.5/10 million),but it still has a higher recurrence rate(12.1%-12.7%),and patients's quality of life decline obviously due to the complications or adjuvant treatment of operation.Thus,the laboratory and clinical research for thyroid cancer still has significant practical significance.Periostin is an extracellular matrix secreted protein secreted by osteoblasts.In recent years,Periostin has been found to expresse in high level in various malignant tumor tissues.The first part of the manuscript,through laboratory research,found in thyroid cancer cells,periostin expression levels were significantly higher than normal thyroid epithelial cells.To explore the biological function of periostin in thyroid carcinoma,shRNA-mediated knockdown of periostin was performed in thyroid carcinoma cell lines,after culturing for 3 and 5 days,periostin-depleted cells showed a significant reduction of proliferation and tumor formationin comparison with control cells in vitro.Thyroid carcinoma cells stably expressing periostin or control shRNA were inoculated subcutaneously into nude mice and gave rise to xenograft tumors.Downregulation of periostin dramatically retarded the formation of subcutaneous tumors compared to the control group in vivo.Through invasive experiments found that periostin knockdown also reduce the invasion of thyroid carcinoma cells significantly.Western blot analysis showed that the expression of TSHR in thyroid cancer cells was reduced after periostin knockdown,and the expression of TSHR was restored by activating the Akt pathway,suggesting that periostin induced TSHR expression through the Akt pathway.The proliferation and invasion of thyroid cancer cells were restored by enforced expression of TSHR in periostin knockdown thyroid cancer cells.Thus,our experiments suggest that periostin plays an important role in the development,proliferation,migration,and invasion of thyroid carcinoma,demonstrating that periostin-mediated Akt/TSHR pathway promotes thyroid cancer aggressiveness.The significance of this study is to provide a potential target for the treatment of thyroid cancer.Papillary thyroid microcarcinoma(PTMC)has a better prognosis compared to most malignancies,but its treatment stratege,especially whether it is needed to performe routinely central lymph node dissection has still been in controversial.It is reported that in papillary thyroid microcarcinoma,the larger tumor size often suggests a higher possibility of lymph node metastasis.In the second part of the manuscript,359 cases of papillary thyroid microcarcinoma treated by our hospital Patients were retrospectively analyzed,and a ROC curve was carried out to determine the cut-off value of the tumor size for predicting the risk of central lymph node metastasis in the papillary thyroid microcarcinoma in preoperative ultrasound images,which indicated 0.575 cm was the cut-off value.Throughing other clinical and pathological indicators,it is confirmed that the cut-off value has a certain role in distinguishing.In the third part of the manuscript,data pertaining to 541 clinically lymph node-negative PTMC patients who underwent thyroid surgery in our hospital between January 2010 and December 2013 were retrospectively analyzed.According to histopathological evidence of central lymph node involvement,patients were divided into central lymph node metastasis(CLNM)positive and CLNM negative groups;risk factors for CLNM were identified statistically.Results shwed LNM was found in 148(27.4%)patients.Gender,age,tumor size,multifocality,and extrathyroidal extension were significantly different between CLNM positive group and CLNM negative group.On multivariate analyses,male sex,age<45 y,extrathyroidal extension and multifocality were independent risk factors for CLNM.
Keywords/Search Tags:thyroid cancer, periostin, PTMC, CLNM
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