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Expression, Diagnostic And Prognostic Value Of UHRF1 In Colorectal Cancer

Posted on:2016-01-10Degree:MasterType:Thesis
Country:ChinaCandidate:L F WuFull Text:PDF
GTID:2284330461971954Subject:Internal Medicine
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Objective: Colorectal cancer is one of most common malignant tumors in the world, with a high incidence in males, especially. Its main pathological type is colorectal Adenocarcinoma(CRC). In our country, the morbidity and mortality of has respectively been up to the fourth and fifth. Moreover, the number of cases maintains a growing tend. Looking for the early and prognosis biomarkers of CRC could help the early diagnosis and accurately classify prognostic risks for patients to promote the study of molecular mechanisms and treatment. UHRF1 is associated with important biological processes of tumor cell proliferation, cell cycle regulation, apoptosis and chemotherapy sensitivity. Aimed to explore the diagnosis and prognosis values of UHRF1, our study prepare to examin its expression in CRC tissues, which will benefit the research of its role during cancer development. Methods: This study collected the specimens of 201 cases of CRC tissues and its paired tissues with morphologically normal glandular epithelium of operation margins(paracancerous tissues). Then we examined the expression of UHRF1 by tissue microarray immunohistochemical technique(TMA-IHC), and also analyzed the difference of positive rates between tumor and paracancerous tissues, correlation between the overexpression and clinical pathological parameters, accessory diagnostic value and prognosis value of colorectal cancer by respectively using paired samples t-test, bilateral χ2 test analysis, ROC Curve, and Kaplan-Meier survival analysis with Cox regression analysis. Results: UHRF1 showed high frequency expression in carcinoma tissues, whereas low detectable in paracancerous tissues(P < 0.01). The rate of weak, moderate and high positive expression were 15.4%(31/201), 12.4%(25/201) and 26.4%(53/201) in tumors, respectively. The total positive rate was up to 54.2%(109/201). Regarding clinical significance, the frequency of high UHRF1 expression in cancer tissue in the proximal colon, distal colon, and rectum were 35.3%(18/51), 61.7%(29/47), 60.2%(62/103), which showed a significant difference among the positive rates in different parts of colorectal cancer tissues(P = 0.008). But meanwhile, there were no obvious statistical correlations between UHRF1 expression and other clinicopathological parameters, such as tumor type, degree of differentiation, clinical stage. The sensitivity, specificity and Youden Index were 54.2%, 90.1%, 44.3% while AUC in the ROC Curve was 0.742. Kaplan-Meier survival curve indicated that the overall survival(OS) of patients was shorter when UHRF1 was high expression in CRC tissues(P = 0.023). Multivariate Cox regression model determined that UHRF1(P = 0.008), tumor differentiation(P = 0.011), lymph node metastasis(P = 0.005) were independent prognostic factors of postoperative colorectal cancer patients. Conclusion: UHRF1 present higher expression in CRC tissues than paracancerous tissues as well as distal colorectal tumor than proximal colon cancer. Detection of this protein might support accessory diagnosis of CRC patients. Expression of UHRF1 is associated with prognosis and proved a independent prognostic factor, which might provide a new target for individual therapy in the future.
Keywords/Search Tags:colorectal cancer, immunohistochemistry, biomarkers, accessory diagnosis, prognosis
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