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The Relationship Between Growth Factor Receptor-bound Protein 2 Expression And The Progression And Prognosis Of Colorectal Cancer

Posted on:2017-01-10Degree:MasterType:Thesis
Country:ChinaCandidate:Z C KangFull Text:PDF
GTID:2334330491463978Subject:Surgery
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Colorectal cancer incidence is creasing rapidly and CRC is becoming a malignance which threaten human life and health seriously.This phenomenon results from the comprehensive effect about environment?heredity?lifestyle?diet ?mentality and so on.1.2 million patients are diagnosed with CRC annually and more than 60 thousand of them died from CRC.Morbidity rate of man is higher than female and middle-aged and elderly people is higher than teenager.Nowadays,many researchers reckon that CRC is caused with gene mutation of normal cell through methylation and developed gradually from neoplasm.According to statistical research,there is a trend pathogenic site appeared from left to right in CRC.Primary and Single therapeutic method of surgery was replaced by complex therapy with surgery?chemotherapy?targeted therapy and so on.It's effective to use chemotherapy on patients with surgery to prevent from relapse,but severe side effect are expected from the chemotherapy itself.What is more serious is that escessive thermotherapy exert an adverse influence on patients than cancer.Overall,it's crucial to investigate novel and efficient biomarker for diagnosing ? predicting diseases and providing patients reasonable therapy.Therapy and prognosis in CRC is decided by pathological staging,but there is obviously difference on survival time for patients with the same pathological staging.Some patients with early staging occur to cancer relapse than those with late staging.Recently,biomarkers in CRC is becoming a hotspot and there are many biomarkers with poor specificity and low clinical value.Consequently,it's obligatory to find good-specificity and high-clinical value.As an adaptor protein,GRB2 expression affect directly cell proliferation and differentiation and many researches suggest that GRB2 unusual expression in malignancies is more pregnant for patients in prognosis and therapy.This research explore that the relationship between GRB2 and genesis and prognosis in CRC with a large number of samples ?complete cases?longer follow-up time and so on by immunohistochemical detection?RT-PCR and Western blot.Part ?The relationship between GRB2 expression and the genesis and prognosis of colorectal cancerObjective:To evaluate the correlation between GRB2 expression and the genesisand prognosis of colorectal cancer(CRC).Methods : GRB2 expression and its location were examined by immunohistochemisty(IHC)in CRC tissue microarray(containing complete information about relapse and survival)established by ChangHai hospital.According to the clinical information of the patients,we analysed the relationship between GRB2 expression and clinicopathologic factors(including age?sex?disease location,etc)by t-test,chi-square test and so on.We researched whether GRB2 expression has an effect on the patients' survival by Kaplan-Meier analysis.Factors contributing to prognosis were investigated with the univariate and multivariate of Cox analysis.Result:GRB2 was mainly expressed in the nucleus and cytoplasm of epithelial cell in CRC.There were no significant difference between GRB2 expression and these clinicopathologic factors namely age?sex?disease location?differentiation grade?TNM stage ? adjuvant chemotherapy and Serum CA19-9 in the nucleus and cytoplasm.High-GRB2 expression was related observably to the lymph nodes examined in the cytoplasm and the Serum CEA in the nucleus.Compared with low-GRB2 patients,high-GRB2 patients had shorter disease-free and overall survival.High-GRB2 expression independently predicted a short disease-free survival(HR=2.664;P=0.015)and overall survival(HR=2.574;P=0.019).Conclusion:There was a close connection between the high-GRB2 expression and the genesis of CRC.High-GRB2 expression independently predicts an unfavorable post-operative prognosis.Part ? GRB2 promote cell proliferation in CRCObjective:To evaluate whether GRB2 promote cell proliferation in CRC.Methods:The efficiency of GRB2 transfection was measured by Western blot and RT-PCR.Cell proliferation was detected by Clone formation.Results:GRB2 was knockdown significantly estimated by Western blot and RT-PCR.There was a correlation between GRB2 and cell proliferation in CRC.Conclusion:GRB2 promote cell proliferation in CRC.
Keywords/Search Tags:colorectal cancer, GRB2, unfavorable post-operative prognosis
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