IGF-1R和VEGFR2蛋白在结直肠癌组织中的表达及其临床意义

Expression and Clinical Significance of IGF-1R and VEGFR2 Protein in Colorectal Cancer Tissue

目的:观察胰岛素样生长因子1受体(IGF-1R)和血管内皮细胞生长因子受体2(VEGFR2)蛋白在结直肠癌组织中的表达,并探讨其临床意义。方法:选择2011年1月-2012年12月在我院行手术治疗的结直肠癌患者98例,收集其肿瘤组织和癌旁组织,采用免疫组化链霉菌抗生物素蛋白-过氧化物酶连接法检测其IGF-1R和VEGFR2蛋白的表达水平,采用逆转录聚合酶链反应法检测两者m RNA的表达水平;考察IGF-1R和VEGFR2蛋白表达与结直肠癌患者临床病理特征的相关性,以及其对术后辅助化疗患者4年无疾病生存率的影响。结果:结直肠癌患者肿瘤组织中IGF-1R和VEGFR2蛋白的阳性表达率分别为66.3%和60.2%,而癌旁组织中均未见其表达,组间比较差异均有统计学意义(P<0.05)。肿瘤组织中IGF-1R m RNA和VEGFR2 m RNA的相对表达量均显著高于癌旁组织,组间比较差异均有统计学意义(P<0.05),且两者m RNA在肿瘤组织中的表达水平呈正相关(r=0.729,P<0.05)。IGR-1R蛋白的表达与患者的性别、年龄、肿瘤部位、有无脉管癌栓形成无关(P>0.05),而与肿瘤组织学分级、浸润深度和有无淋巴结转移有关(P<0.05);VEGFR2蛋白的表达与患者的性别、年龄无关(P>0.05),而与肿瘤部位、组织学分级、浸润深度、有无淋巴结转移和脉管癌栓形成有关(P<0.05)。98例结直肠癌患者中,14例患者术后未行化疗;其余84例患者4年无疾病生存率为76.2%(64/84),其中IGF-1R蛋白阴性表达、VEGFR2蛋白阴性表达患者的4年无疾病生存率(82.8%、78.8%)均显著高于其阳性表达者(72.7%、74.5%),差异均有统计学意义(P<0.05)。采用多因素Logistic回归分析对性别、年龄、组织学分级、肿瘤部位、浸润深度、有无淋巴结转移和脉管癌栓形成等因素进行校正后,IGF-1R和VEGFR2蛋白的表达仍与患者4年无疾病生存率相关[校正比值比(OR)分别为2.31、2.15,95%置信区间分别为(0.57,4.15)、(0.45,4.03),P<0.05]。结论:结直肠癌患者肿瘤组织中IGF-1R和VEGFR2蛋白及m RNA的表达明显增强,且蛋白的表达与肿瘤组织学分级、浸润深度、有无淋巴结转移等因素以及术后辅助化疗患者的预后有关。两者的联合检测可为结直肠癌患者的靶向治疗提供参考。

OBJECTIVE： To observe the expression of IGF-1R and VEGFR2 in colorectal cancer tissue, and to explore its clinical significance. METHODS： Totally 98 colorectal cancer patients underwent surgery were selected from our hospital during Jan. 2011-Dec. 2012. The tumor tissue and paracancerous tissue were collected. The expression of IGF-1R and VEGFR2 protein were detect- ed by immunohistochemical SP method. The mRNA expression of both were detected by RT-PCR. The correlation of the expression of IGF-1R and VEGFR2 protein with clinical pathological characteristics of colorectal cancer patients were investigated, and its effects on 4-year disease-free survival rate of postoperative assisted chemotherapy patients were also investigated. RESULTS： The positive rates of IGF-1R and VEGFR2 protein expression in colorectal cancer tissue were 66.3% and 60.2% respectively, but their expression was not found in paracancerous tissue, with statistical significance （P〈 0.05）. Relative expression of IGF-1R mRNA and VEGFR2 mRNA in tumor tissue were significantly higher than paracancerous tissue, with statistical significance （P〈 0.05）. There was positive correlation between their mRNA expression in tumor tissue （r = 0.729, P〈 0.05）. The expression of IGR-1R protein was independent from pa- tient＇ s gender and age, tumor location and formation of vascular tumor thrombus （P〉 0.05） ; but it was associated with the histological grading, depth of invasion and lymph node metastasis （P〈 0.05）. The expression of VEGFR2 protein had nothing to do with patient＇ s gender and age （P〉 0.05）, but it was associated with tumor location, histological grading, depth of invasion, lymph node metastasis, and formation of vascular tumor thrombus （P〈 0.05）. Among 98 colorectal cancer patients, 14 patients didn＇t underwent chemotherapy after surgery; and 4-year disease-free survival rate of other 84 patients was 76.2 % （64/84）. Four-year disease-free survival rates of TGF-1R protein negative expression and VEGFR2 protein negative expression patients （82.8 %, 78.8 % ） were significantly higher than those of positive expression patients （72.7 %, 74.5% ）, with statistical significance （P〈0.05）. The multiple factor Logistic regression analysis was used to correct gender, age, histological grading, tumor location, depth of invasion, lymph node metastasis, and forma- tion of vascular tumor thrombus; the expression of IGR-1R and VEGFR2 protein were still associated with 4-year disease-free survival rate [adjusted OR were 2.31, 2.15 ; 95 % CI were （0.57,4.15）, （0.45,4.03） ; P〈 0.05]. CONCLUSIONS ： The expression of IGF- 1R, VEGFR2 protein and mRNAs increase significantly in colorectal cancer tissue; the protein expression is associated with histological grading, depth of invasion, lymph node metastasis and the prognosis of postoperative assisted chemotherapy patients. Their examina- tion can provide reference for target therapy for eoloreetal cancer patients.