Expression And Significance Of SIRT3 And Skp2 Protein In Colorectal Polyps And Colorectal Cancer In Clinic

Part One:pression and Significance of SIRT3 protein in Colorectal Polyps and Colorectal Cancer in ClinicBackgroundColorectal cancer is one of the most common cancers worldwide,more than 1.25 million newly diagnosed patients with colorectal cancer each year, and 600,000 people died of the disease. Sirt3 is the family member of the third class deacetylase Sirtuins.It may regulate cell survival and apoptosis by adjusting the synthesis of a variety of biological molecules.In recent years, studies have found abnormal expression of Sirt3 in the lung, breast, esophageal, gastric, liver and other tumors.The expression of Sirt3 is associated with the degree of malignancy and the prognosis of the patients.At present, report about the expression of Sirt3 in development of colorectal cancer is rare.ObjectiveTo detect the expression levels of SIRT3 in colorectal carcinoma,colorectal adenomas(tubular adenoma,mixed pattern of adenoma,villous adenoma),colorectal hyperplastic polyps and normal colorectal mucosa,to explore the role and value of SIRT3 during the development of colorectal carcinoma,and it provide the new possible clue for the early diagnosis and therapy in colorectal cancer.MethodsDetect the location and expression of SIRT3 in 50 specimences of colorectal carcinoma tissues,80 specimences of colorectal adenomas (including 30 specimences of tubular adenoma,30 specimences of mixed pattern of adenoma,20 specimences of villous adenoma),30 specimences of colorectal hyperplastic polyps and 20 specimences of normal colorectal mucosa tissues by immunohistochemistry. Analysis the correlation between SIRT3 with the clinic and pathologic data of colorectal carcinoma patients including pathology type,invasive depth,with or without nodal metastasis and distant metastasis.Results1.The results of the immunohistochemistry were that the positive expression rates of the SIRT3 protein in normal colorectal mucosa,colorectal hyperplastic polyps,colorectal adenomas and colorectal carcinoma tissues were 75%,73.3%,48.75%,40%,respectively,with significant differences among them(P<0.05).2.The results of the immunohistochemistry were that the positive expression rates of the SIRT3 protein in tubular adenoma,mixed pattern of adenoma and villous adenoma were 66.7%, 46.7%,25%,respectively,with significant differences among them(P<0.05).3.The correlation of the expression levels of SIRT3 with the clinical pathological information of the patient with colorectal carcinoma show that:there was a significant correlation between the exprresion rates of SIRT3 with pathology type,invasive depth,including nodal metastasis and including distant metastasis,respectively,with significant differences among them(P<0.05).There was no obvious difference in age,sex and tumour size (P>0.05)Conclusion1.In the sequences of normal colorectal mucosa,colorectal hyperplastic polyps,colorectal adenomas and colorectal carcinoma,the expression of SIRT3 decreased,showing that SIRT3 had a significant value in the development of colorectal carcinoma. And there was a significant correlation between the exprresion rates of SIRT3 with pathology type,invasive depth and including nodal metastasis,no obvious difference in age,sex and tumour size.2. As the villous grows higher in adenoma,the expression of the SIRT3 presented a gradual downward trend. SIRT3 was an important reference index for malignant change of colorectal polyps,and detecting the expression of SIRT3 can provide some help for the early diagnosis of the colorectal carcinoma.Part Two:Expression and Significance of Skp2 protein in Colorectal Polyps and Colorectal Cancer in Clinic and the relationship between SIRT3 and Skp2 BackgroundColorectal cancer is one of the most common cancers worldwide,more than 1.25 million newly diagnosed patients with colorectal cancer each year, and 600,000 people died of the disease.Skp2 is S-phase kinase-associated protein.It plays a role as an important component of the E3 ubiquitin ligase complexes.It mainly mediates cell cycle regulation by degrading cyclins.While skp2 can recognize substrate proteins for ubiquitin—protein degradation, on the other hand, it also regulates closely by its upstream APC/Cdhl.In recent years, studies have found that Sirt3 can deacetylate Skp2.At present, report about the simultaneous detection of Sirt3 and Skp2 in development of colorectal cancer is rare.ObjectiveTo detect the expression levels of Skp2 in colorectal carcinoma,colorectal adenomas(tubular adenoma,mixed pattern of adenoma,villous adenoma),colorectal hyperplastic polyps and normal colorectal mucosa,and analyze the relationship between SIRT3 and Skp2 in the progresion of Colorectal Cancer.Materials and MethodsDetect the location and expression of Skp2 in 50 specimences of colorectal carcinoma tissues,80 specimences of colorectal adenomas (including 30 specimences of tubular adenoma,30 specimences of mixed pattern of adenoma,20 specimences of villous adenoma),30 specimences of colorectal hyperplastic polyps and 20 specimences of normal colorectal mucosa tissues by immunohistochemistry. Analysis the correlation between Skp2 with the clinic and pathologic data of colorectal carcinoma patients including pathology type,invasive depth,with or without nodal metastasis and distant metastasis.Analysis the correlation between SIRT3 and Skp2 in the development of colorectal carcinoma.Results1.The results of the immunohistochemistry were that the positive expression rates of the Skp2 protein in normal colorectal mucosa,colorectal hyperplastic polyps,colorectal adenomas and colorectal carcinoma tissues were 10%,13.3%,28.75%,66%,respectively,with significant differences among them(P<0.05).2.The results of the immunohistochemistry were that the positive expression rates of the Skp2 protein in tubular adenoma,mixed pattern of adenoma and villous adenoma were 10%, 23.3%,65%,respectively,with significant differences among them(P<0.05).3. Analysis the correlation of the expression levels of Skp2 with the clinical pathological information of the patient with colorectal carcinoma show that:there was a significant correlation between the exprresion rates of Skp2 with pathology type,invasive depth including nodal metastasis and including distant metastasis,with significant differences among them(.P< 0.05).There was no obvious difference in age,sex and tumour size (P>0.05)4.The correlation coefficient of SIRT3 and Skp2 is:r=-0.01(P<0.05).the expression of Skp2 is negatively related with the SIRT3 protein in colorectal caner.Conclusion1.In the sequences of normal colorectal mucosa,colorectal hyperplastic polyps,colorectal adenomas and colorectal carcinoma,the expression of Skp2 rasied,showing that Skp2 had a significant value in the development of colorectal carcinoma. And there was a significant correlation between the exprresion rates of Skp2 with pathology type,invasive depth and including nodal metastasis,no obvious difference in age,sex and tumour size.2. As the villous grows higher in adenoma,the expression of the Skp2 presented a gradual upward trend. Skp2 was an important reference index for malignant change of colorectal polyps,and detecting the expression of Skp2 can provide some help for the early diagnosis of the colorectal carcinoma.3.The relationship between SIRT3 and Skp2 is that the expression of Skp2 is negatively related with the SIRT3 protein in colorectal caner.