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Expression And Clinical Significance Of NLRC3 In Human Colorectal Tumors

Posted on:2020-10-24Degree:MasterType:Thesis
Country:ChinaCandidate:Z Q CangFull Text:PDF
GTID:2404330572977078Subject:Surgery
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ObjectiveIn China,one of the most common malignant tumors of colorectal cancer,the incidence rate is second only to lung cancer,stomach cancer and liver cancer.With the improvement of China's economic development and living standards,the changes brought about by the living environment and diet structure have led to the continuous increase of the incidence of colorectal cancer in China.With the advancement of modern science and technology,new diagnostic and therapeutic tools have emerged,including pre-cancerous screening,surgery,multidisciplinary treatment,chemotherapy and radiotherapy.However,most patients with colorectal cancer,especially in the advanced stage of the tumor,have a lower 5-year survival rate and a higher recurrence rate.With the continuous research on the development of tumors,research in the molecular field has proposed three theories,including the generation of cancer cells caused by normal gene damage,the abnormal activation of oncogenes and the mutation of tumor suppressor genes.Dysfunctional.NLRC3(NLR family CARD domain containing 3,comprising three effector nucleotide-binding oligomerization domain)NLR is a(nucleotide-binding domain leucine-rich repeats,nucleotide-binding oligomerization domain and)family NLRC3(also known as CLR16.2 or NOD3)is a poorly characterized member of the NLR family and has been identified in genomic screening to encode a leucine-rich repeat(LRR(leucine rich repeat)The gene of the leucine from the complex sequence))and the nucleotide binding domain of the protein Studies have found that mice lacking NLRC3 are prone to colitis and colorectal tumorsThe role of NLRC3 is most prominent in colorectal cells.One of its effects is that it inhibits the activation of the mTOR signaling pathway and inhibits cell proliferation and stem cell-derived organoid formation.NLRC3 binds to PI3Ks and blocks the activation of PI3K-dependent kinase AKT upon binding to growth factor receptor or Toll-like receptor 4.These findings reveal a key role for NLRC3 as a mTOR pathway inhibitor,inhibiting the development of colorectal tumors.The focus of this study was on the expression of NLRC3 in human colorectal tumors and its relationship to clinical parametersMethods1.Immunohistochemical SP(Strptavidin-Perxidase,streptavidin-peroxidase)method was used to detect the expression of NLRC3 in 116 cases of colorectal malignant tumors,60 cases of adjacent tissues and 10 cases of adenomas.And study its relationship with clinical pathological parameters.Judging criteria:Two unsuspecting and experienced pathologists read the film and judged the results.Qualitative determination of NLRC3 expression was performed based on the coloring ratio and degree of staining of tumor cells.The coloring ratio of the integrated cells and the degree of staining were superimposed on each of the scores to determine the final score Divide it into 4 levels2.After the first radical resection of colorectal cancer,the normal mucosa with a negative margin of 5 cm or more from the tumor was negative.Western Blot was used to detect the expression of NLRC3 protein in fresh colorectal tumor tissues and normal mucosa tissues.The experimental results were determined by Image-pro plus Version 6.0.1 image analysis system with ?-actin as internal control3.The results were analyzed by SPSS23.0 statistical software.The relationship between the expression of NLRC3 and clinicopathological factors was analyzed by ?2 test,p<0.05 was considered statistically significantResults1.Immunohi stochemi stry:(1)The positive expression rate of NLRC3 in 116 cases of colorectal malignant tumors was 75.86%(88/116),and the positive expression rate in normal colorectal mucosa was as high as 100%;in normal mucosa,The strong positive rates of adenoma,well-differentiated,moderately differentiated carcinoma,and poorly differentiated carcinoma were 61.67%,40.0%,37.5%,21.4%,and 0%,respectively,and the expression rate was significantly correlated with tumor differentiation(p=0.001).(2)NLRC3 expression was not significantly associated with gender,age,tumor location,depth of invasion,metastasis,tumor morphology,and clinical TNM stage(p>0.05)2.Western blot:Image-pro plus Version 6.0.1 image analysis system scan absorbance value,?2=689.23,o<0.01,the difference in expression is significantConclusionThe expression of NLRC3 protein is closely related to the degree of differentiation of colorectal tumors,and NLRC3 is down-regulated in colorectal tumors.The expression of NLRC3 was negatively correlated with the degree of tumor differentiation,suggesting that NLRC3 may be involved in the development and progression of human colorectal tumors.Its detection has certain value for the early diagnosis,treatment and prognosis of colorectal tumors.
Keywords/Search Tags:Colorectal cancer, Immunohistochemistry, Western blotting NLRC3 gene, NLRC3 prorein
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