CDX-2、VEGF-C在胃癌组织中的表达及其与预后关系的临床意义
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摘要
目的
     以往有些研究报道VEGF-C在胃癌淋巴转移起着重要的作用,但是VEGF-C和CDX-2在胃癌组织中的联合表达尚未有文献报道。本研究旨在分析血管内皮生长因子-C(VEGF-C)和同源异型框转录因子-2(CDX-2)在胃癌组织中的表达及其临床病理特征,探讨其与胃癌预后的关系。
     方法
     选取南昌大学第三附属医院2006年1月~2007年8月胃镜或术后病理证实的88例胃癌标本。入选标本术前均未进行放化疗,术后行常规的放化疗。实验组中男53例,女35例,年龄25-78岁,平均年龄57.6±1.31岁;按Lauren分型,肠型胃癌62例,弥漫性胃癌17例,混合型胃癌9例;按分化程度,高中分化型胃癌12例,中分化型胃癌27例,低分化型胃癌49例;按浸润深度分,T1+T2者32例,T3+T4者56例;按有无区域淋巴结转移,N1 31例,N2 24例,无淋巴结转移33例;远处转移者5例,无远处转移83例;按临床分期,Ⅰ+Ⅱ期40例,Ⅲ+Ⅳ期48例。选取20例同时期胃镜检查的正常胃粘膜作为对照组,男13例,女7例,年龄28~76岁,平均年龄54.2±1.35岁,两组病例在年龄性别构成无明显差异。采用免疫组织化学方法检测CDX-2和VEGF-C的表达情况及与胃癌组织分化、浸润和转移的关系,并随访患者生存情况,应用cox回归分析探讨CDX-2和VEGF-C胃癌组织中的表达对胃癌患者预后的影响。
     结果
     1.60例患者获得随访材料。我们研究结果得出:1、CDX-2和VEGF-C在胃癌组织中的阳性表达率比正常胃粘膜高,分别为46.5%和61.3%,均具有统计学意义(x2=4.374, P=0.012);2、VEGF-c与肿瘤分化程度、浸润深度、淋巴结转移相关(P<0.05),而CDX-2表达Lauren分期、浸润深度及TNM分期有关(P<0.05);3、通过kaplan-meier生存曲线和Cox回归多因素分析,CDX-2与VEGF-C在胃癌组织中的表达中提示CDX-2(+)/VEGF-C(-)患者预后最好,而CDX-2(-)/VEGF-C(+)预后最差;4、CDX-2、VEGF-C与胃癌患者预后存在负相关。
     结论
     检测CDX-2、VEGF-C胃癌组织中的的表达,有助于判断患者的预后,CDX-2与VEGF-C联合检测可能是胃癌患者预后的预测指标。
Purpose:It was reported that VEGF-C played an important role in lymphatic metastasis of gastric cancer.However,VEGF-C and CDX-2 express commonly in gastric cancer have not yet reported in the literature. The purpose of Our research is to analyze the expression of Caudal type homeobox-2 (CDX-2), vascular endothelial growth factor-C (VEGF-C) and their clinical pathological features in gastric carcinoma,and to explore their relationship with the prognosis of gastric cancer.
     Methods:We choose 88 cases of gastric cancer confirmed gastroscopy or post-operative pathology as the experimental group, and from 88 cases of gastric cancer taking 20 adjacent normal mucosa tissues as the control group. All tissues detected by immunohistochemistry,and have not apply Chemoradiotherapy before operation, The experimental group is consist of 53 males and 35 females, aged 25-78years, mean age 57.6±1.31 years; According to Lauren classification, It was made up of 62 cases of intestinal-type gastric cancer,17 cases of diffuse gastric cancer,9 cases of mixed-type gastric cancer; According to Tumor differentiation,there are 12 cases of high differentiate gastric cancer,27 cases of differentiated-type gastric cancer,49 cases of poorly differentiated gastric cancer; According to the depth of invasion,32 cases in T1+T2,56 cases in T3+T4; According to regional lymph node metastasis, there are 31 N1,24 N2 and 33 cases without lymph node metastasis; 5 cases have distant metastasis, and 83 patients without distant metastasis; According to clinical stage,there are 40 patients inⅠ+Ⅱand 48 inⅢ+Ⅳ. In the Control group, There are 13 males and 7 females, range from 28 years to 76 years, and their mean age is 54.2±1.35 years. The two groups are no significant difference in age and gender. We analyze the relations of CDX2、VEGF-C and gastric differentiation, invasion and metastasis,and survival time were followed up in most patients. Then we apply cox regression to analyze CDX-2 and VEGF-C expression with their prognosisin gastric carcinoma patients.
     Results:60 patients were followed-up. We get the results as this:1.The expression of CDX-2 and VEGF-C protein is higher in gastric carcinoma than that in normal mucosa,respectively 46.5% and 59.4%, there is statistically significant (x 2=4.374, P=0.012), The expression of VEGF-C is relation with Lauren, invasion depth and TNM staging (P<0.05), whereas VEGF-C is relation with tumor differentiation, invasion depth,lymph node metastasis (P<0.05); 3. By analyzing kaplan-meier survival curve and cox regression, we find that the expression of CDX-2 (+)/VEGF-C (-) with the best prognosis in patients, while the expression of CDX-2 (-)/VEGF-C (+)has the worst prognosis.5.lymph node metastasis may be an independent predictor in gastric cancer.
     Conclusion:The expression of CDX-2, VEGF in gastric cancer tissues can help predict the prognosis of gastric cancer, CDX-2 and VEGF-C joint-detection may be prognostic indicators of gastric cancer patients.
引文
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    综上所述,在胃癌的生长及转移过程中,对肿瘤血管形成的分子基础研究已经成为一个热门。近年来由于分子生物学技术的发展,VEGF的特点及生物学功能也越来越清楚,VEGF呈现出治疗胃癌的应用价值,这一领域的研究值得进一步深入与拓展。
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