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Expression And Significance Of LSD1 And Wnt Pathway Related Proteins In Colorectal Cancer

Posted on:2021-04-01Degree:MasterType:Thesis
Country:ChinaCandidate:H LiuFull Text:PDF
GTID:2404330626960201Subject:Surgery
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Objective: The purpose of this study is to detect LSD1 and Wnt signal pathway related proteins expression in colorectal cancer,paired paracancerous tissues and normal colorectal tissues and corresponding cell lines.Methods:1.The expression of LSD1 and Wnt signaling pathway related proteins was analyzed by using the data set of colon cancer and normal colon tissue in TCGA database,and the differentially expressed proteins in colon cancer were initially screened.2.Immunohistochemistry was applied to explore the expression of LSD1,?-catenin,Ecadherin,LEF1 and MMP9 in 36 cases of colorectal cancer and matched paracancerous tissues and 10 cases of normal colorectal tissues.And weanalyzed the the expression of respective proteins and clinical pathological features by Fisher's exact test methods.Spearman correlation analysis was used to analyze the correlationship between LSD1 and?-catenin,E-cadherin,LEF1,MMP9,respectively.To detect the expression of LSD1,?-catenin,E-cadherin,LEF1 and MMP9 in 5 cases of colon cancer and matched paracancerous tissues.T-test was used to analyze the difference of protein expression between two groups.3.Western Blot was also applied to detect the expression of LSD1,?-catenin,E-cadherin,c-myc and cyclin D1 in colon cancer cell lines HT-29,HCT-116 and normal colon epithelial cell line NCM460.The T-test was adopted as statistical method,too.Results:1.The analysis of TCGA database showed that compared with normal tissues,the expression of LSD1,?-catenin,LEF1,MMP9,c-myc and cyclin D1 in colon cancer was dramatically elevated,while E-cadherin was significantly down-regulated.2.The positive expression rates of LSD1,?-catenin,E-cadherin,LEF1 and MMP9 in colorectal cancer tissues were 88.9%(32/36),75%(27/36),66.7%(24/36),69.4%(25/36),61.1%(22/36),respectively.In paracancerous tissues,the respectivepositive expression rates were 63.9%(22/36),36.1%(13/36),91.7%(33/36),22.2%(8/36),27.7%(10/36),and the positive rates in normal tissues were 50%(5/10),20%(2/10),100%(10/10),20%(2/10),10%(1/10),respectively.The differences were all statistically significant(P<0.05).Among these data,there was no significant difference in the expression of LSD1,?-catenin,E-cadherin,LEF1 and MMP9 in colorectal cancer tissues with different sex,age,location,TNM stage,lymph node metastasis and pathological grade.There was a positive correlation between the expression of LSD1 and ?-catenin in colorectal cancer(rs=0.348,P=0.04),and a negative correlation between LSD1 and E-cadherin in colorectal cancer(rs =-0.345,P=0.039),but no significant correlation between LSD1 and LEF1,MMP9,respectively.3.The expression of LSD1,?-catenin,LEF1 and MMP9 in colon cancer was statistically higher than that in paracancerous tissues,while E-cadherin was significantly reduced.4.Among the cellular level,compared with the normal colon epithelial cell line NCM460,the expression of LSD1,?-catenin,c-myc and cyclin D1 in colon cancer cell lines HT-29 and HCT-116 was significantly up-regulated,while the expression of E-cadherin was suppressed.All of the differences were statistically significant(P<0.05).Conclusion:1.In colorectal cancer,the expression of LSD1 is positively correlated with of ?-catenin,the essential role in Wnt signal pathway,and negatively correlated with the expression of E-cadherin,suggesting that there may be an interaction between LSD1 and Wnt signal pathway,which may synergistically participate in tumorigenesis.2.Compared with adjacent tissues and normal colorectal tissues,LSD1,?-catenin,LEF1 and MMP9 in colorectal cancer tissues was significantly over-expressed,while the expression of E-cadherin was reduced,suggesting that these five proteins may be involved in the occurrence and development of colorectal cancer.3.In comparison to normal colon epithelial cells,the expression of LSD1,?-catenin,c-myc and cyclin D1 increased in colon cancer cells,while E-cadherin was reduced.The potential interaction mechanism between LSD1 and Wnt signaling pathway needs to be further studied,which is expected to provide new concepts for colorectal cancer therapies.
Keywords/Search Tags:Lysine-specific demethylase 1(LSD1), colorectal cancer, Wnt signal pathway
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