Dissertation
Dissertation > Medicine, health > Oncology > Gastrointestinal Cancer

Study on the Function of Angiogenesis in Gastrointestinal Carcinoma Invasion and Metastasis

Author WeiJianMin
Tutor LiuXinLan
School Ningxia Medical University
Course Oncology
Keywords Ang-2 Tie-2 VEGFR-2 MVD Gastrointestinal cancer Angiogenesis Immunohistochemistry Western blot
CLC R735
Type Master's thesis
Year 2010
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The purpose of detecting gastrointestinal cancer tissue vascular Epo -2 (of angiogenin in-2, Ang-2) and its specific tyrosine kinase receptor-2 (tyrosine kinase with immunoglobulin-like and epidermal growth factor homology domains, Tie- 2) and vascular endothelial growth factor receptor -2 (vascular endothelial growth factor receptor-2, VEGFR-2) expression, and analysis of their relationship with clinicopathologic characteristics, tumor microvessel density (Microvessel Density, MVD), and prognosis, investigate whether it can be used as forecast gastrointestinal cancer invasion and metastasis and prognostic molecular biomarkers. Methods immunohistochemistry (Immunohistochemistry, IHC) Detection of Ningxia Medical University Hospital, 118 patients hospitalized gastrointestinal cancer patients (64 cases of gastric cancer, colorectal cancer, 54 cases) from January 2002 to November 2008 cancer tissue, 40 cases of cancer and adjacent normal tissue (from the cancer tissue ≥ 5cm) and 40 cases of benign gastrointestinal disease lesions of Ang-2, Tie-2, VEGFR-2 expression; of CD34 marker microvascular. Western blot (western blot) Ningxia Medical University Hospital inpatient surgical treatment of 76 cases of gastrointestinal cancer tissue of cancer patients (40 cases of gastric cancer, colorectal cancer, 36 cases) were detected from May 2008 to November 2008, 40 cases of cancer and adjacent normal tissue (from the cancer tissue ≥ 5cm) and 40 cases of benign gastrointestinal disease lesions of Ang-2, Tie-2, VEGFR-2 expression. Results (1) immunohistochemistry part: 1) Ang-2, Tie-2 and VEGFR-2 in gastrointestinal cancer tissue positive expression rate were 74.58%, 69.49% and 61.02%, respectively; adjacent normal tissue The positive expression rate of 25.00%, 17.50% and 17.50%; gastrointestinal benign tissue positive expression rate of 35.00%, 32.50% and 32.50%, respectively; adjacent normal three expression in cancer tissues and cancer expression in benign tissue and gastrointestinal lesions was statistically significant (P lt; 0.05); paracancerous expression in normal tissue and benign lesions had no statistical significance (P gt; 0.05). 2) Ang-2 expression in gastrointestinal cancer depth of invasion, lymph node metastasis, distant metastasis, clinical stage was positively correlated (P lt; 0.05); Tie-2 expression in gastrointestinal cancer distant metastasis, clinical stage related (P lt; 0.05); VEGFR-2 expression and gastrointestinal cancer, depth of invasion, lymph node metastasis, distant metastasis, clinical stage (P lt; 0.05); logistic multivariate regression analysis showed that distant metastasis clinical stage were associated with Ang-2, Tie-2 and VEGFR-2 expression (P lt; 0.05); infiltration depth of Ang-2 expression related (P lt; 0.05). 3) radical 5 years after recurrence and metastasis and without recurrence metastasis Ang-2, Tie-2 and VEGFR-2 expression differences were statistically significant (P lt; 0.05). 4) Kaplan-Meier survival analysis showed that: Ang-2, Tie-2 and VEGFR-2 expression and overall survival period related to the expression of the 5-year survival rate was significantly higher than that of the negative to positive expression (P lt; 0.05). 5) Ang-2, Tie-2 and VEGFR-2 expression and patients within five years distant metastasis (P lt; 0.05), and overall survival in patients with negative expression 5-year survival rate was significantly higher than positive expression (P lt; 0.05). 6) two or three factors of expression were significantly higher than the single factor positive expression rate, the difference was statistically significant (P lt; 0.05), all these three negative and the expression of a single factor positive 5-year survival rate than those The co-expression of two or three factor (P lt; 0.05). 7) Ang-2 in gastrointestinal cancer tissue expression of CEA, CA199 was positively correlated (P lt; 0.05) were positively correlated (P lt; Tie-2 and VEGFR-2 in gastrointestinal cancer tissue expression of CEA ; 0.05). Gastrointestinal cancer patients CEA negative expression of Ang-2 and Tie-2 of VEGFR-2 positive expression rate was 59.09% (13/22), 50.00% (11/22), 40.91% (9/22); gastrointestinal cancer patients CA199 negative expression of Ang-2, Tie-2, VEGFR-2 positive expression rate were 64.29% (18/28), 60.71% (17/28), 50.00% (14/28). 8) Ang-2, Tie-2, VEGFR-2 positive expression in gastrointestinal cancer tissue and MVD was positively correlated (P lt; 0.05). 9) Ang-2, Tie-2 and VEGFR-2 in gastrointestinal cancer expression pairwise comparisons showed a positive correlation (P lt; 0.05). (2) Western blot experiment part: 1) Ang-2, Tie-2 and VEGFR-2 in gastrointestinal cancer tissue positive expression rate were 76.32%, 72.37% and 63.16%; adjacent normal tissue The positive expression rate of 30.000%, 22.50% and 22.50%; gastrointestinal benign tissue positive expression rate of 40.00%, 37.500% and 32.50%, respectively, three in the cancer tissue and adjacent normal tissue expression and cancer The expression in the gastrointestinal benign lesions was statistically significant (P lt; 0.05); paracancerous expression in normal tissue and benign lesions had no statistical significance (P gt; 0.05). 2) Ang-2 expression in gastrointestinal cancer, depth of invasion, lymph node metastasis, and clinical stage was positively correlated (P lt; 0.05); Tie-2 expression in gastrointestinal cancer clinical stage was positively related (P lt; 0.05); VEGFR-2 expression in gastrointestinal cancer, depth of invasion, lymph node metastasis, and clinical stage was positively correlated (P lt; 0.05); logistic multi-factor regression analysis showed that the depth of invasion and clinical stage and Ang-2 expression related (P lt ; 0.01); clinical stage and Tie-2 expression (P lt; 0.01); lymph node metastasis and clinical stage VEGFR-2 expression (P lt; 0.05). 3) Ang-2, Tie-2 and VEGFR-2 expression in gastrointestinal cancer was positively correlated (P lt; 0.05). (3) immunohistochemistry and Western blot analysis: two methods simultaneous detection of Ang-2, Tie-2 and VEGFR-2 expression in gastrointestinal cancer tissue, the two detection methods Kappa values ??were 0.756,0.638 , 0.672; consistent rate of 91.83%, 84.48%, and 86.89%, respectively. Conclusion (1) the presence of Ang-2, Tie-2 and VEGFR-2 protein expression in gastrointestinal cancer tissue. (2) Ang-2 expression in gastrointestinal cancer depth of invasion, lymph node metastasis, distant metastasis, clinical stage, MVD and radical 5 years after recurrence and metastasis were positively correlated, and gastrointestinal cancer 5-year survival , showed that Ang-2 and the biological behavior of the cancer of the gastrointestinal tract are closely related, as predicted gastrointestinal cancer invasion and metastasis and to determine the prognosis molecular biomarkers. (3) Tie-2 expression in gastrointestinal cancer distant metastasis, clinical stage, MVD and radical 5 years after recurrence and metastasis were positively correlated, and 5-year survival rate of cancer of the gastrointestinal tract, showed that Tie-2 participate in regulation of gastrointestinal cancer angiogenesis occurred as predicted gastrointestinal cancer invasion and metastasis and prognosis of one of the markers of Molecular Biology. (4) VEGFR-2 expression in gastrointestinal cancer depth of invasion, lymph node metastasis, distant metastasis, clinical stage, MVD and radical 5 years after recurrence and metastasis were positively correlated, and the 5-year survival rate of cancer of the gastrointestinal tract show that VEGFR-2 is involved in the regulation of gastrointestinal cancer angiogenesis as predictors of gastrointestinal cancer invasion and metastasis and prognosis of one of the markers of molecular biology. (5) in gastrointestinal cancer tissue Ang-2, Tie-2 and VEGFR-2 alone three protein expression and co-expression, co-expression mainly associated with the 5-year survival rate of the patients showed that the joint detection variety of angiogenic factors may increase the detection rate of invasion and metastasis to better reflect the patient's prognosis. (6) of Ang-2, Tie-2 and VEGFR-2 expression was associated with postoperative distant metastasis-related and associated with 5-year survival rate of patients, indicating that the three early stages of distant metastases occur in gastrointestinal cancer that played a role, as predicted the invasion and metastasis of gastrointestinal cancer early marker of molecular biology. (7) Ang-2 expression and CEA, CA199 showed a positive correlation, Tie-2 and of VEGFR-2 expression and CEA were positively correlated, CEA, CA199 expression negative caught presence of Ang-2, Tie-2 and of VEGFR-2 positive expression Description detection of CEA, CA199 negative expression of Ang-2, Tie-2, VEGFR-2 may improve the detection rate of early invasion and metastasis. (8) Ang-2, Tie-2 and VEGFR-2 expression in gastrointestinal cancer were positively correlated, indicating which all involved in gastrointestinal cancer angiogenesis, and there are synergies in this process, suggesting that the tumor angiogenesis is a complex process involving more than one factor. (9) immunohistochemistry and Western blot two methods qualitative and quantitative detection of gastrointestinal cancer tissue Ang-2, Tie-2, VEGFR-2 expression results are consistent and can be used in clinical and research.

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