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The Expression Profiling Of SIRT1 In Tongue Squamous Cell Carcinoma With Different Pathological Grades And The Relevant Research Of Its Clinical Significance

Posted on:2019-07-30Degree:MasterType:Thesis
Country:ChinaCandidate:H S LiuFull Text:PDF
GTID:2404330545982949Subject:Oral Medicine
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Objectives: Oral squamous cell carcinoma(OSCC)is the sixth largest in the world and the third most common malignant tumor in developing countries,with an annual increase of up to 500,000 cases.The five-year survival rate is about 50%.Tongue squamous cell carcinoma(TSCC)is one of the most common OSCC,accounting for about 80% of the total.Due to the traditional treatment of tongue cancer caused great damage on the swallowing,language function and face of patients,the search for new treatment has been urgent.SIRT1,a NAD+-dependent histone deacetylase,can be involved in many physiological and pathological processes of life,including the regulation of cell stress response,metabolism,aging and apoptosis,which are closely related to tumorigenesis,stage classification and prognosis.Studies have found that the expression of SIRT1 is decreased in a variety of malignant tumors,including skin cancer,colon cancer and ovarian cancer,suggesting that SIRT1 may have tumor suppressor role.However,some scholars think that the upregulation of SIRT1 in prostate cancer,breast cancer and gastric cancer is associated with carcinogenesis.Therefore,SIRT1 may play a dual role in the occurrence and development of malignant tumors.It has been confirmed that the expression of SIRT1 is decreased in OSCC.However,the expression of SIRT1 in TSCC of different pathological grades is not clear in the literature.The purpose of this study was to investigate the expression and distribution of SIRT1 in TSCC of different pathological grades and to provide a new strategy and basis for molecular targeted therapy of tongue cancer.Methods: We selected 42 patients with TSCC from patients undergoing oral and maxillofacial surgery in the second hospital of Dalian Medical University.All patients have complete medical records,without prior anti-cancer treatment,and signed informed consent.According to the World Health Organization's oral cancer histological grading standards(1997)to determine the pathological grade,collecting specimens and tissuesafter surgery.1.Immunohistochemical analysis was used to detect the expression and distribution of SIRT1 in 42 cases of TSCC(including 22 cases of well-differentiated TSCC,11 cases of moderately-differentiated TSCC,9 cases of poorly-differentiated TSCC)and their paracancer tissues.2.Western blot was used to detect the expression of SIRT1 in 9 cases of TSCC tissues(including 3 cases of well-,moderately-,and poorly-differentiated TSCC)and corresponding paracancerous tissues.Results: 1.Immunohistochemical analysis showed that:Intensely decreased staining of SIRT1 was found in all differentiated grade TSCC(P <0.01).At the same time,the level of SIRT1 was closely related to the differentiation of TSCC,and the expression of SIRT1 was also significantly down-regulated with the decrease of differentiation.The expression of SIRT1 was significantly decreased by 6.47%(P <0.01),26.79%(P <0.01),53.70%(P <0.01)in well-differentiated,moderately-differentiated and poorly-differentiated TSCC tissues,respectively.In TSCC and adjacent tissues,SIRT1 was mainly distributed in the nucleus.In the moderately and the poorly-differentiated TSCC,SIRT1 also existed in some of the cytoplasm.2.The results of Western Blot showed that the expression of SIRT1 was significantly lower in TSCC than that in paracancerous tissues(P <0.01),which was consistent with the immunohistochemical analysis results.Conclusion: Based on the above data,we concluded that the expression of SIRT1 in TSCC was significantly down-regulated and was significantly decreased with the increase of the malignancy of tongue cancer.It suggests that SIRT1 may play an important role in the occurrence and development of TSCC.With the development and practice in clinical anti-tumor therapy of SIRT1 agonist,our findings are expected to provide a new strategy and basis for the molecular targeted therapy of tongue cancer.
Keywords/Search Tags:SIRT1, TSCC, SIRT1 agonist, Targeted therapy of cancer
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