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The Expression And Significance Of MicroRNA-7/FAK Axis In Colorectal Cancer

Posted on:2014-01-30Degree:MasterType:Thesis
Country:ChinaCandidate:J HuangFull Text:PDF
GTID:2254330425958374Subject:Internal Medicine
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Background:Colorectal cancer is one of the most common malignant tumors at home andabroad, the global incidence is on the rise.Clinical diagnosis of colorectal cancer oftenhave followed with lymph node metastasis. Whether or not with Lymph nodemetastasis is closely related with the prognosis of patients. The treatment effect ofcolorectal cancer still can not achieve satisfactory results, especially treatment andprognosis of metastatic colorectal cancer is poor, which often seriously affect thequality of life, and the invasiveness and metastasis behavior mechanism of action isnot fully understood. Domestic and international shows that the molecular targettreatment of signal pathway in cell proliferation and metastasis to may improve theprognosis of cancer, exploring the pathogenesis of tumors and finding a cure has beenthe focus of research.The process of metastasis of tumor cells includes the reorganization of thecytoskeleton, Cell movement related to cellular pseudopod formation, between cellsand extracellular matrix adhesion and detachment, cell migration, etc. FAK proteinhas close relationship with cell invasion and metastasis. FAK and its phosphorylatedproteins can mediate expression of cell motility related proteins and induce epithelialmesenchymal transformation process,which plays an important role in colorectalcarcinogenesis and metastasis. Studies have shown that FAK is the target genes ofmicroRNA-7, microRNA-7through a combination of3’non-coding region of mRNAof FAK targeted the FAK protein translation and can inhibit the growth of a variety oftumor cell invasion and metastasis. Therefore, this experiment was designed toexplore the interaction of the microRNA-7/FAK axis in colorectal cancer, and wewould provide new targets for the research on colorectal cancer molecular therapy.Objectives:The aim of this experiment is to investigate the related expression andsignificance of microRNA-7/FAK axis in colorectal cancer by in vivo and analyze therelationship of expression of microRNA-7and FAK and Ki-67with the proliferationand metastasis of colorectal cancer by combining with patients clinical data and elucidate the role of microRNA-7/FAK axis in the pathogenesis of colorectal cancer,and search new targets for the treatment of colorectal cancer.Methods:Colorectal cancer tissue specimens were collected, the tumor tissues andcorresponding adjacent tissues were fixed by formaldehyde and frozen at-80℃storage respectively, and recorded the patients clinical pathological data. Throughimmunohistochemistry we detect the expression of FAK, p-FAK and proliferationrelated protein Ki-67in tumor tissue. By method of real-time PCR we detectexpression of microRNA-7in tumor tissue and adjacent normal tissue. Through thepatient clinical data combined with the characteristic of expression of FAK, p-FAK,Ki-67and microRNA-7. We analyze the correlation between expression of FAK,p-FAK, Ki-67, microRNA-7and different indexes of patient clinical data.Results:1. The positive expression rate of FAK, p-FAK protein in colorectal cancer tissuewas respectively75%,65%. The expression of FAK, p-FAK was significantly higherthan that of the adjacent normal tissue (P<0.05). Expression of FAK and p-FAK withlymph node metastasis in colorectal cancer showed significantly higher level thanwithout lymph node metastasis(P<0.05).In colorectal cancer, the expression rate ofFAK, p-FAK of low differentiation and undifferentiated group was significantlyhigher than that of moderately differentiated and high differentiation group (P<0.05).The expression of FAK, p-FAK in tumor tissues of patients with clinical TNM stageⅢ/Ⅳ was significantly higher than that of patients with stage I/II. But expression ofFAK and p-FAK had no relationship with the age、sex、tumor position.2. The Ki-67positive rate in colorectal cancer tissue was58.33%which wassignificantly higher than that of the adjacent tissue (P<0.05). The expression of Ki-67and FAK expression have significant difference in colorectal cancer, and have certaincorrelation (p<0.05), but there was no significant correlation between expression ofKi-67and expression of p-FAK.3. The expression of microRNA-7in colorectal cancer tissues was significantlylower than that of the corresponding adjacent tissue, and there was statisticallysignificant difference between the two groups (P<0.05).4. The expression of microRNA-7in cancer tissues of patients with TNM stage Ⅲ/Ⅳ was significantly lower than that of patients with stage I/II, and expression ofmicroRNA-7with lymph node metastasis in colorectal cancer was significantly lowerthan that of without lymph node metastasis(P<0.05). But level of microRNA-7hadno relationship with the age、sex、tumor position.5. The low expression group of microRNA-7in colorectal cancer had39cases,inwhich there were33cases of positive expression of FAK, and6cases of negativeexpression of FAK. The high expression group of microRNA-7had21cases, inwhich there were33cases of positive expression of FAK, and6cases of negativeexpression of FAK. The low expression of microRNA-7level was negativelycorrelated with expression level of FAK in colorectal cancer (r=-0.303,P<0.05).6. In the low expression group of microRNA-7in colorectal cancer there were29cases of positive expression of p-FAK, and10cases of negative expression ofp-FAK. In the high expression group of microRNA-7there were10cases of positiveexpression of p-FAK, and11cases of negative expression of p-FAK. The lowexpression of microRNA-7level was negatively correlated with expression level ofp-FAK in colorectal cancer (r=-2.67,P<0.05). But microRNA-7expression had nocorrelation with Ki-67expression (P>0.05).Conclusion:1. The expression of FAK, p-FAK was increased in colorectal cancer. Theexpression of FAK and p-FAK was related to differential degree of tumor, lymphnode metastasis and TNM staging, but had no relationship with the age、sex、tumorposition.2. The expression of microRNA-7in colorectal cancer tissues was significantlylower than that of the corresponding adjacent tissue. The low expression level ofmicroRNA-7negatively correlated with the high expression of FAK and p-FAK incolorectal cancer. The expression level of microRNA-7in colorectal cancer wasclosely related to TNM staging and lymph metastasis of colorectal cancer, but had norelationship with the age, sex, tumor position and differential degree of tumor.3. microRNA-7/FAK is related to the development and progression of colorectalcancer, which may be one of the pathogenesis of colorectal cancer.
Keywords/Search Tags:Colorectal cancer, Lymph node metastasis, microRNA-7, Focal adhesionkinase, p-FAK, Ki-67
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