Smad4信号通路蛋白与Cortactin蛋白在卵巢肿瘤中的表达及意义

发布时间：2018-05-21 08:59

本文选题：Smad4 + Cortactin　；参考：《泰山医学院》2014年硕士论文

【摘要】：目的本课题旨在检测卵巢上皮性肿瘤中Smad4及Cortactin基因及蛋白的表达，探讨上皮性卵巢癌组织中Smad4、Cortactin的表达与临床病理特征的关系，以及组织中Smad4及Cortactin表达的相关性。进一步探索上皮性卵巢癌发生及发展过程中Smad4信号通路的作用，以及Smad4对于细胞运动的影响，为判断预后提供依据，为临床治疗提供新靶点。方法本研究采用上皮性卵巢癌为研究对象，以卵巢良性上皮性肿瘤、正常卵巢组织为对照组，利用实时荧光定量PCR法（Method of Real-time quantitative reversetranscriPtion Polymerase chain reaction）检测Smad4及Cortactin mRNA的表达情况，免疫组织化学SP三步法检测Smad4及Cortactin蛋白在不同卵巢组织中的表达。结果 1．上皮性卵巢癌组织中Smad4mRNA的相对含量低于卵巢良性上皮性肿瘤及正常对照（P㩳0.05），Smad4mRNA在卵巢良性上皮性肿瘤组织中的表达是上皮性卵巢癌组织中的5.75倍。Smad4mRNA表达与卵巢癌组织学分级、FIGO分期、淋巴结转移及腹水呈负相关（P㩳0.05）。 2．上皮性卵巢癌组织中Cortactin mRNA的相对含量高于卵巢良性上皮性肿瘤及正常对照（P＜0.05）；Cortactin mRNA表达与卵巢癌组织学分级、FIGO分期相关（P㩳0.05），与年龄、淋巴结转移及腹水无关（P＞0.05）。 3．Smad4蛋白主要定位于肿瘤细胞胞浆内，部分位于细胞核，呈现出棕黄色或棕褐色颗粒。上皮性卵巢癌组织中Smad4蛋白阳性表达率为44.00㳠，呈弱阳性；而卵巢良性上皮性肿瘤与正常对照组织中Smad4蛋白阳性表达率为70.00㳠以上，表达呈强阳性。Smad4蛋白阳性表达率与卵巢癌组织学分级、FIGO分期、淋巴结转移及腹水有关（P＜0.05）。 4．Cortactin蛋白定位于肿瘤细胞的细胞质及细胞膜，部分位于细胞核。上皮性卵巢癌组织中Cortactin蛋白阳性表达率为73.30㳠，表达多为强阳性；卵巢良性上皮性肿瘤及正常对照组织中Cortactin蛋白阳性表达率不足25㳠，呈弱阳性；Cortactin蛋白的表达仅与卵巢癌组织学分级有关（P＜0.05），，与FIGO分期、淋巴结转移、腹水及年龄无关（P＞0.05）。 5．Spearman相关性分析结果显示：上皮性卵巢癌组织中Smad4和CortactinmRNA表达之间存在中度负相关关系（r=－0.541, P=0.005）；而组织中Smad4和Cortactin蛋白表达之间呈高度线性负相关（r=－0.738, P=0.000）。 6．上皮性卵巢癌Smad4蛋白表达阳性者平均生存期为40.6±4.2个月（95%CI,35.3-43.0月），阴性表达者平均生存期为26.1±5.3个月（95%CI,24.7-30.6月），差异有统计学意义（P=0.026），Cortactin蛋白表达阳性者平均生存期为19.5±1.2个月（95%CI,14.6-21.4月），阴性表达者平均生存期为34.5±4.3个月（95%CI,22.1-25.9月），差异有统计学意义（P=0.017）。 7．单因素生存分析显示：上皮性卵巢癌患者Smad4阳性表达者较阴性表达者具有显著生存优势（x2=4.944，P=0.026）。而Cortactin阴性表达者较阳性表达者具有显著生存优势（x2=5.739，P=0.017）。COX回归模型进行多因素分析，两者均为上皮性卵巢癌的独立预后因素，其中smad4阴性表达：P=0.001RR=5.412（95%CI，2.719-6.112），Cortactin阳性表达：P=0.001RR=6.452（95%CI，2.289-7.512）。结论 1．上皮性卵巢癌组织中Smad4mRNA及蛋白表达存在缺失现象，Smad4表达缺失与卵巢癌组织学分级、FIGO分期、淋巴结转移及腹水呈负相关，单因素生存分析显示Smad4阳性表达者具有显著生存优势，多因素分析显示Smad4表达为独立预后因素。说明Smad4作为TGF-β信号转导通路中的关键环节，其表达缺失在卵巢癌恶性进展中可能发挥推动作用，Smad4阴性表达者预后不良。 2．上皮性卵巢癌组织中Cortactin mRNA及蛋白表达明显高于卵巢良性肿瘤，Cortactin mRNA表达与卵巢癌组织学分级及FIGO分期相关，而Cortactin蛋白表达仅与卵巢癌组织学分级相关。单因素生存分析显示Cortactin阴性表达者具有显著生存优势，多因素分析显示Cortactin表达为独立预后因素。说明肿瘤细胞分化越差，细胞运动活性越强，作为重要的细胞骨架蛋白，Cortactin表达上调与卵巢癌的不良预后密切相关。 3．上皮性卵巢癌组织中Smad4和Cortactin mRNA表达之间存在中度负相关关系（r=－0.541, P=0.005）；而Smad4和Cortactin蛋白表达之间呈高度线性负相关（r=－0.738, P=0.000）。两者之间的高度相关性表明：TGF-β信号传导通路可能通过Smad4调控细胞骨架蛋白，Cortactin可能是Smad4途径重要的下游靶基因，肿瘤细胞可能通过Smad4-Cortactin途径调节肿瘤细胞运动，从而影响了肿瘤细胞的侵润和转移。Smad4-Cortactin细胞运动途径可能具有潜在的生物学治疗价值。
[Abstract]:Purpose

The purpose of this study was to examine the expression of Smad4 and Corsinn genes and proteins in epithelial ovarian tumors and to investigate the relationship between Smad4 and Corsinn expression in epithelial ovarian carcinoma .

method

The expression of Smad4 and Corsinn mRNA was detected by real - time quantitative reverse transcription polymerase chain reaction ( Real - time quantitative reverse transcription polymerase chain reaction ) , and the expression of Smad4 and Corsinn protein in different ovarian tissues was detected by immunohistochemical SP three - step method .

Results

1 . The relative content of Smad4mRNA in epithelial ovarian carcinoma was lower than that in ovarian benign epithelial tumor and normal control ( P ? 0.05 ) . The expression of Smad4mRNA in ovarian benign epithelial tumor tissue was 5.75 times in epithelial ovarian carcinoma . Smad4mRNA expression was negatively correlated with histological grade , FIGO stage , lymph node metastasis and ascites ( P ? 0.05 ) .

2 . The relative content of Corsinn mRNA in epithelial ovarian carcinoma was higher than that in ovarian benign epithelial tumor and normal control group ( P < 0.05 ) .
The expression of Corsinn mRNA was correlated with histological grade of ovarian cancer and FIGO stage ( P ? 0.05 ) , and was not related to age , lymph node metastasis and ascites ( P > 0.05 ) .

3 . Smad4 protein was mainly localized in the cytoplasm of tumor cells , partly in nucleus , brown or brown . The expression rate of Smad4 protein in epithelial ovarian carcinoma was 44.00 ?
The positive expression rate of Smad4 protein in ovarian benign epithelial tumor and normal control group was 70.00 % . The positive expression rate of Smad4 protein was correlated with histological grade of ovarian cancer , FIGO stage , lymph node metastasis and ascites ( P < 0.05 ) .

4 . Corsinn protein was localized in the cytoplasm and cell membrane of tumor cells , partly in the nucleus . The positive expression rate of Corsinn protein in epithelial ovarian carcinoma was 73.30 ? , and the expression was strongly positive ;
The positive expression rate of Corsinn protein in ovarian benign epithelial tumor and normal control group was less than 25 ?
The expression of Corsinn protein was only related to histological grade of ovarian cancer ( P < 0.05 ) , which was not related to FIGO stage , lymph node metastasis , ascites and age ( P > 0.05 ) .

The results showed that there was a moderate negative correlation between Smad4 and CortactinmRNA expression in epithelial ovarian carcinoma ( r = - 0.541 , P = 0.005 ) .
There was a highly linear negative correlation between the expression of Smad4 ( r = - 0.738 , P = 0.000 ) .

6 . The average survival time of Smad4 protein in epithelial ovarian carcinoma was 40.6 卤 4.2 months ( 95 % CI , 35.3 - 43.0 months ) . The average survival time of negative expression was 26.1 卤 5.3 months ( 95 % CI , 14.6 - 21.4 months ) . The average survival time of negative expression was 34.5 卤 4.3 months ( 95 % CI , 22.1 - 25.09 months ) , and the difference was statistically significant ( P = 0 . 017 ) .

7 . Single - factor survival analysis showed that Smad4 positive expression in epithelial ovarian cancer patients had significant survival advantage ( x2 = 4.944 , P = 0.026 ) . However , the positive expression of Corsinn negative expression had significant survival advantage ( x2 = 5.739 , P = 0 . 017 ) . The COX regression model was analyzed by multivariate analysis , both of which were independent prognostic factors of epithelial ovarian cancer , with smad4 negative expression : P = 0.001RR = 5.412 ( 95 % CI , 2.719 - 6.112 ) , Cornun positive expression : P = 0.001RR = 6.452 ( 95 % CI , 2.289 - 7.512 ) .

Conclusion

1 . There was a negative correlation between Smad4 mRNA and protein expression in epithelial ovarian carcinoma . Smad4 expression was negatively correlated with histological grade of ovarian cancer , FIGO stage , lymph node metastasis and ascites . Single factor survival analysis showed that Smad4 expression was independent prognostic factor .

2 . Corsinn mRNA and protein expression in epithelial ovarian carcinoma were significantly higher than that in ovarian benign tumor , Corsinn mRNA expression was correlated with histological grade and FIGO stage of ovarian cancer . The single - factor survival analysis showed that Corresponds n - negative expression was independent prognostic factor .

3 . There was a moderate negative correlation between the expression of Smad4 and Corsinn mRNA in epithelial ovarian carcinoma ( r = - 0.541 , P = 0.005 ) .
There was a highly linear negative correlation between Smad4 and Corsinn protein expression ( r = - 0.738 , P = 0.000 ) . The high correlation between them indicates that TGF - 尾 signaling pathway may regulate the cytoskeletal proteins through Smad4 . Corresponds n may be an important downstream target gene in Smad4 pathway . The tumor cells may regulate tumor cell movement through the Smad4 - Corresponds n pathway , thus affecting the invasion and metastasis of tumor cells . Smad4 - Cornun cell movement pathway may have potential biological treatment value .
【学位授予单位】：泰山医学院
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R737.31

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