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Expression Of ING4and HIF-1α Gene In Colorectal Cancer And Its Significance

Posted on:2015-11-19Degree:MasterType:Thesis
Country:ChinaCandidate:H Z ZhaoFull Text:PDF
GTID:2284330431492747Subject:Surgery
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Background and PurposeColorectal cancer (carcinoma of rectum) is a malignant tumor of the largeintestine, the current epidemiological study found that the incidence of colorectalcancer accounts for two-thirds of colorectal cancer, and its incidence is increasingyear by year, its incidence has gradually tend to develop younger, degree ofdifferentiation in the percentage of high grade type is also increasing. Currenttreatment programs for colorectal cancer is surgical excision, supplementary drugchemotherapy, radiotherapy and biological treatment, but also to achieve itstherapeutic effect expected level.5-year survival rate of patients with colorectalcancer surgery in about60%of early colorectal cancer after curative resection,5-year survival rate of80%to90%, showing that early detection and early treatmentof colorectal cancer in the rectum the survival rate of cancer patients after surgeryplays a vital role. Currently the majority of colorectal cancer patients in the countrywere found to have come in late, and accompanied by distant metastasis of malignanttumors, which will not only increase the difficulties and risks to the treatment ofsurgical resection, but also on quality of life and prognosis of patients withpostoperative negative impact of direction. So, look for the early detection of colorectal cancer and the ways and means prognosis becomes extremely necessaryresearch from the molecular point of view to explore the ways and means of alsocontinue to move forward. The occurrence and development of malignant tumorsrequires the interaction of cancer-promoting genes and tumor suppressor genescommon result at different times and in different environments, the occurrence anddevelopment of colorectal cancer also need to work together in these two genes[1].Growth inhibitory factor4(ING4) as a potential tumor occurrence and developmentof gene suppression, has been widely studied and reported. From yeast to humans,ING4highly conserved in evolution characteristics, the nucleotide sequencehomology higher[2], inhibits tumor angiogenesis and tumor cell growth, induction ofapoptosis, such as biological activity, studies have shown that, ING4p53-dependent manner and inhibit cell growth, to induce apoptosis, which may control thep53protein acetylation, eventually restrain cell growth and proliferation, whileenhancing the activity of the p53gene in a variety of tumor cells lack of mutations inperformance, reduced or absent[3-4]. ING4can make the cells in a state of contactinhibition, thereby inhibiting tumor occurrence and development. ING4can alsoreduce the activity of IL-8expression, thereby inhibiting tumor angiogenesis. ING4can also inhibit the movement of cancer cells and induce apoptosis of tumor celltargets, and ultimately play a role in anti-tumor specificity. ING4gene expression oftumor cells can increase the sensitivity to chemical agents. Hypoxia-inducible factor-1α (HIF-1α) is the center of the tumor cells adapt to hypoxia regulatory factors,overexpression of HIF1-α is found in many human cancer cells, and the formation ofblood vessels and tumor growth and metastasis. Currently on ING4and HIF-1αresearch and other malignancies reported in the visible, but both normal tissue in therectum and colorectal cancer tissues, and the relationship between research andclinical pathology between the two indexes between the and reported in the literatureare relatively rare, this experiment ING4protein expression and HIF-1α protein incolorectal cancer tissues and normal rectal tissue through the use of SP were detectedby immunohistochemistry, and then analyzes the relationship betweenclinicopathological parameters between the experimental results and the relationshipbetween the expression in colorectal cancer, and to explore ING4protein and HIF-1α protein significance in the occurrence and development of colorectal cancer in theprocess, so as to provide new ideas at an early stage colorectal cancer diagnosis,treatment and prognosis of clinical assessment.MethodsIn this study, immunohistochemical method to detect133cases of colorectalcancer tissues,76cases more than10cm away from the outer edge of foci normalrectal tissue ING4and HIF-1α expression, and analysis of ING4and HIF-1α incolorectal cancer and normal rectum differences in the organization and expression ofboth expression in colorectal cancer tissue correlation, and also analyzed therelationship between ING4and HIF-1α expression and clinicopathologicalparameters in colorectal cancer in between.Results1ING4expression in colorectal cancer tissues was71/133(53.4%) wassignificantly lower than normal rectal tissue65/76(85.5%), statistically significantwas different (χ2=21.985, P<0.001). The expression of HIF-1α in colorectal cancertissues was93/133(69.9%) was significantly higher than normal rectal tissue32/76(42.1%), the difference was statistically significant (χ2=15.571, P <0.001).2In the133cases of colorectal cancer tissues, ING4and HIF-1α proteinexpression with age, sex were not related (P>0.05); ING4and HIF-1α proteinexpression, respectively, with the degree of differentiation, Dukes stage and lymphnode metastasis was significantly correlation (P <0.05).3colorectal cancer tissues of71patients ING4positive expression in31casesof HIF-1negative expression; while in62patients with negative expression of ING4,there HIF-1α expression53cases. The Spearman correlation analysis in colorectalcancer in ING4negatively correlated with the expression of HIF-1α (r=-0.317, χ2=13.369, P=0.000).Conclusion1ING4low expression in colorectal cancer tissues, HIF-1α expression incolorectal cancer tissues, both expressed in normal tissues and colorectal cancer in therectum abnormalities suggesting that the process plays an important role in thedevelopment of colorectal cancer in. 2ING4expression and tumor extent in colorectal cancer tissue differentiation,Dukes stage and lymph node metastasis was significantly correlated; HIF-1αexpression and the degree of tumor differentiation in colorectal cancer tissues, Dukesstage and lymph node metastasis was significantly correlated, indicating that both inthe course of colorectal cancer with disease progression, and to some extent, canreflect the degree of malignancy of the tumor further judgment on the future play arole in guiding patients.3ING4and HIF-1α expression in colorectal cancer tissues were negativelycorrelated, suggesting that both the incidence of colorectal cancer in the complexprocess of development, respectively, and played a role in promoting the suppressionand can be used as molecular detection of colorectal cancer-related markers, makingcomprehensive evaluation and assessment of patients with colorectal cancerprognostic factor.
Keywords/Search Tags:Colorectal cancer, ING4, HIF-1α, Immunohistoehemistry
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