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DPC4’s Expression in Non-Small Cell Lung Cancer and Its Relationship with Angiogenesis and Cell Apoptosis

Author: KeZunFu
Tutor: ZhuRunQing
School: Wuhan University
Course: Pathology and Pathophysiology
Keywords: Lung carcinoma DPC4 Apoptosis Angiogenesis Immunohistochemical technique
CLC: R734.2
Type: Master's thesis
Year: 2005
Downloads: 42
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Abstract


Objective:In this experiment, we selected 52 cases of NSCLC and 19 carcinomal adjacent lung tissues as experimental objects.Through detecting the expression of DPC4, TGF-βl、 P21wafl、 VEGF and CD34 and their mutual relationships, we provided theoretical datas for NSCLC’s occurrence and progression.Methods:1.The expressions of DPC4、TGF-β 1、 P21wafl、VEGF and CD34 were examined by SP immunohistochemical technique.2.To detect the cell apoptosis through TUNEL.3.To detect mutation of the extrons 1、 3、 8、 11 through PCR-SSCP.4.A11 the datas were analysized by the statistical software SPSS11.5, maentime, the positive results of DPC4、 TGF-β1、 P21wafl and VEGF were carried out through Chi-aquare or Fish’s Exact Test. The reciprocal relationships among them were analyzed by Tow-tailed Pearson Bivariate.The relationships between DPC4 and MVD\ AI were checked by T Test.The possibility was thought significant as long as it was under 0.05 level.Results:1. Expression of TGF- β 1: Its total positive rate in NSCLC was 40.39% (21/52), while in 19 carcinomal adjacent tissues only 2 cases were positive whose positive rate was higher than that in NSCLC with statistical significance(P<0.017).It was significant(P<0.01) between the positive rate of squamous caicinoma 16.00%(4/25) and that of adenocarcinoma 62.96%(17/27).The positive rates among high, middle and low differentiation were 35.71%(5/14), 44.44%(8/18) and 40.00%(8/20) respectedly without significance (P>0.05) among them.In 17 cases with lymph node metastasis, the positive rate was 82.35%(14/17), and it was significant(P<0.01)if compared with that in35 cases without lymph node metastasis20.00%(7/35).2.Expression of DPC4: Its positive rates were 89.5% (17/19) in carcinoma adjacent tissues and 63.5%(33/52) in NSCLC respectedly, between which statistically it was significant(P<0.05) .The positive rate in adenocarcinoma was higher than that in squamous carcinoma, however, statistically it was not significant(P>0.05).Its positive expression was not related with differentiated degree(P>0.05).In cases with lymph node metastasis, the positive rate was 29.41%(5/17), which was obviously lower than that 80.00%(28/35) in cases without lymph node metastasis(P<0.001).3.Expression of P2lwafl: In NSCLC group, the positive rate was 48.08%(25/52), which was higher than thatl5.79%(3/19) in carcinoma adjacent tissues with significance(P=:0.014).However, P21wafl ’s positive expression was not correlated with pathological types, differentiated degree and lymph node metastasis(P>0.05).4.DPC4 expression’s relationship with TGF- P 1 and P21waflIn 33 cases with DPC4 positive expression, there were 8 cases positive in TGF- ^ l’s expression, meantime, 6 cases were negative, from which it showed negative correlation between DPC4 and TGF- B l(P=0.001). In 33 cases with DPC4 positive expression, there were 22 cases positive in P21wafl expression, meantime. 16 cases were negative, from which it implied positive correlation between DPC4 and P21W (/*=0.000).5.DPC4 expression’s relationship with VEGF and MVDIn DPC4 negative group, VEGF’s positive rate was obviously higher than that in positive group with clearly negative correlation(P=0.020).In DPC4 positive group, the number of MVD was 43.74±7.25, which was obviously lower than that(61.77±7.09) in negative group with great significance (P<0.001) .6.DPC4 expression’s relationship with AIAI in DPC4 positive group was higher that in negative group with great significance( P <0.05).7.DPC4’s mutation in NSCLCIn 20 NSCLC group, there were 4 cases without extended strip, which were 1 inexon 8, 3 in exon 11 .The rate of DPC4’s complete absence was 20.0% (4/20) .In 20 NSCLC group, there were 6 cases with abnormal strip, which were 1 in exon 1, 3 in exon 2, 2 in exon 8 and 1 in exon 11.The rate of DPC4’s mutation was 30.0%(6/20).Conclusions:1. The overexpression of TGF- 0 > P21WAF1 and the low expression of DPC4 were closely correlated with the occurrence, invasion and metastasis of lung carcinoma.2. The low expression of DPC4 and high expression of P21WAF1 maybe promote the strong expression of TGF- £ reactively.3. Through regulating VEGF’s expression, DPC4 inhibited angiogenesis inderectively, simultaneously, through other factors inhibiting angiogenesis.4. As the important conducting factor of TGF- 3 signal pathway, DPC4’s low expression can influence the apoptosical signal conduct, which promoted decreasing of the number of apoptosical cell.5. As an suppressor gene, DPC4’s complete absence and mutation can promote occurrence of NSCLC.

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