【作者】 刘伟；

【导师】 王欣；

【作者基本信息】 天津医科大学 ， 肿瘤学， 2011， 硕士

【摘要】 目的：通过大样本临床病例的研究,检测CysLTRl和CysLTR2在乳腺癌中的表达情况,并分析CysLTR1和CysLTR2与乳腺癌及预后的关系,评价其是否可作为预后预测分子标志物的临床价值,为寻找新的治疗靶点提供理论依据。方法：采用半定量RT-PCR和实时荧光定量PCR方法,从mRNA水平上检测90例原发乳腺癌组织和30例匹配的癌旁组织中CysLTR1和CysLTR2基因的表达量,并应用Western Blot方法从蛋白水平上进一步证实CysLTR1和CysLTR2的表达情况,分析二者与临床病理学参数之间的关系,以及与乳腺癌患者预后的关系。结果：1.乳腺癌组织CysLTR1和CysLTR2mRNA表达明显低于癌旁组织,两者差异均具有显著的统计学意义(P=0.002和P=-0.000)。乳腺癌组织中CysLTR1mRNA的表达程度与肿瘤大小相关(P=0.013),即肿瘤直径>2cm组表达水平高于直径≤2cm组,而与年龄、组织学分级、淋巴结转移、TNM分期、ER、PR、HER2、PCNA和P53的表达无相关性(P>0.05)。乳腺癌组织中CysLTR2mRNA的表达程度与年龄、肿瘤大小、组织学分级相关(P<0.05),即年龄>50岁的患者乳腺癌组织中CysLTR2mRNA表达高于年龄≤50岁组(P=0.023)；肿瘤直径≤2cm组表达水平高于直径>2cm组(P=0.009)；另外,中分化组CysLTR2mRNA高表达率高于高、低分化组(P=0.011),而与淋巴结转移、TNM分期、ER、PR、HER2, PCNA和P53的表达未发现相关性(P>0.05)。2. Kaplan-Meier生存分析结果显示：CysLTR1mRNA表达水平的高低对本组乳腺癌患者的无病生存并无影响(P=0.205)。而CysLTR2mRNA高表达者的总的无病生存率显著高于低表达水平者(P=0.010)。而无论是在肿瘤直径>2cm的患者中,还是肿瘤直径≤2cm的患者中,CysLTR1mRNA和CysLTR2mRNA的表达量的高低对无病生存率并无影响(P>0.05)。3. Western Blot结果显示：在乳腺癌组织中CysLTR1和CysLTR2均有表达。结论：CysLTR1mRNA的高表达可能与乳腺癌患者病情进展和预后不良相关,但CysLTR1是否为潜在的预后预测标志物仍需大样本资料的进一步研究来证实；CysLTR2mRNA高表达提示预后较好,CysLTR2是潜在的预后预测标志物。更多还原

【Abstract】 Objective:The fact that breast cancer patients with local or distal dissemination exhibit decreased survival, promotes a search for novel mechanisms to suppress such tumor progression. To analyse the relationship between the expression level of CysLTRl mRNA and CysLTR2mRNA and prognosis in breast cancer patients. To identified whether CysLTR1and/or CysLTR2could be molecular markers in predicting the prognosis in breast cancer patients.Methods:Primary breast cancer specimens were obtained from90patients who had undergone surgery at Tianjin Cancer Hospital. Real time PCR was performed to detect the mRNA expression of CysLTR1and CysLTR2in90primary breast cancer tissues, paired30breast cancer tissues and adjacent normal breast tissues. Western blot were used to confirm the protein level of CysLTR1and CysLTR2expression. The relationship of CysLTRl and CysLTR2expression and clinicopathological parameters was studied.Results:1. CysLTRl and CysLTR2mRNA expression level in breast cancer tissue were higher than that in adjacent normal breast tissues (P=0.002and P=0.000). The expression level of CysLTR1mRNA was associated with tumor size. The significant higher level of CysLTRl mRNA expression was seen in large tumor (>2cm) compared to small tumor (≤2cm)(P=0.013). There seemed no relationship between expression of CysLTR1mRNA and other clinico-pathological factors (P>0.05).The expression level of CysLTR2mRNA was related with patient age, tumor size and histological grade (P<0.05).The expression level was significant higher in patients over50years old than in patients less than50years old (P=0.023). The CysLTR2mRNA expression level was significant lower in large tumor(>2cm) than in small tumor(≤2cm (P=0.009). CysLTR2mRNA expression level was increased with histological grades (P=0.011).2. Kaplan-Meier survive analysis showed that the expression of CysLTR2mRNA had strong correlation with disease free survive (P=0.010), but the expression of CysLTR1mRNA had no correlation with disease free survive (P>0.05).3. The protein level of CysLTR1and CysLTR2expression were confirmed in breast cancer patients.Conclusions:The expression of CysLTRl mRNA and CysLTR2mRNA in breast cancer tissue were significant lower compared to it in adjacent normal tissue. The higher CysLTR1expression in breast cancer patients tends to have poor outcome. The higher CysLTR2expression seems to have better outcome and it may be a potiential marker for predicting prognosis in breast cancer patients.更多还原