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叶酸受体α在人脑胶质瘤组织中表达及其临床意义

Changes of folate receptor-a protein expression in human gliomas and its clinical relevance

摘要:

目的 研究叶酸受体α(FR-α)在脑胶质瘤组织中的表达情况及其临床意义.方法 收集2012年3月至2013年3月行手术治疗的胶质瘤患者标本组织共计48例,其中胶质母细胞瘤(WHOⅣ级)12例,星形细胞瘤(WHOⅡ、Ⅲ级)各6例,少突胶质细胞瘤(WHOⅡ、Ⅲ级)各6例,少突星形细胞瘤(WHOⅡ、Ⅲ级)各6例.另取6例颅脑外伤切除的正常脑组织作为对照;取1例胎盘组织(已征得母体及家属同意)作为阳性对照.采用Western blot检测FR-α表达水平并采用£检验比较WHOⅡ级与WHOⅢ级肿瘤中FR-α表达水平的差异.免疫组化方法检测FR-α和Ki-67蛋白在肿瘤组织中的定位与表达情况,并采用Kruskal-Wallis检验比较不同病理级别胶质瘤组织中FR-α和Ki-67细胞阳性率的差异,组间多重比较采用Nemenyi检验.运用Pearson相关分析胶质瘤组织中FR-α表达水平与肿瘤细胞增殖指数Ki-67之间的关系.结果 Western blot结果显示,正常脑组织和少突胶质细胞瘤组织中无FR-α表达;星形细胞瘤组织中FR-α呈高表达,其中Ⅲ级肿瘤组织中表达水平明显高于Ⅱ级(t=4.497,P<0.05);少突星形细胞瘤组织中FR-α亦呈高表达,且Ⅲ级肿瘤组织中表达水平亦明显高于Ⅱ级肿瘤组织(t =2.876,P<0.05);FR-α于胶质母细胞瘤中高表达.免疫组化结果显示,少突胶质细胞瘤组织(Ⅱ和Ⅲ级)与正常脑组织中FR-α呈阴性表达.星形细胞瘤Ⅱ级和Ⅲ级肿瘤组织中FR-α呈阳性表达,Ⅲ级肿瘤细胞FR-α阳性率为57.8%±2.2%,明显高于Ⅱ级肿瘤组织的45.7%±2.3%(x2=3.871,P=0.034).少突星形细胞瘤Ⅱ级和Ⅲ级肿瘤组织中FR-α亦呈阳性表达,Ⅲ级肿瘤组织阳性率为56.5%±5.4%,明显高于Ⅱ级肿瘤组织的37.1%±5.2%(x2=4.454,P=0.021).与其他级别肿瘤相比,胶质母细胞瘤中FR-α的表达水平最高,阳性率为65.0%±4.5%.FR-α阳性率与Ki-67指数呈正相关(r=0.903,P<0.05).结论 少突胶质细胞瘤组织中FR-α表达呈阴性;星形细胞瘤、少突星形细胞瘤和胶质母细胞瘤组织阳性表达FR-α,且FR-α表达水平与肿瘤病理级别和Ki-67指数正相关.FR-α可能成为脑胶质瘤诊断和治疗的特异性靶点.

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abstracts:

Objective To study the expression level of folate receptor α (FR-α) in glioma tissue and its clinical significance.Methods Forty-eight human glioma specimens were collected from patients who underwent surgery from March 2012 to March 2013.These specimens were as follows:12 cases of glioblastoma (WHO Ⅳ),6 cases of astrocytoma of each malignancy grade (WHO Ⅱ,Ⅲ),6 cases of oligodendroastrocytoma of each malignancy grade (WHO Ⅱ,Ⅲ),6 cases of oligodendroglioma of each malignancy grade (WHO Ⅱ,Ⅲ).In addition,6 cases of normal brain tissue resected from brain traumatic patients were taken as negative control,and one case of placental tissue (had got the consent of the parents and their families) was taken as positive control.The expression level of FR-α in tumor tissues was evaluated by Western blot analysis.The results of Western blot analysis were analyzed by t-test.The expression level of FR-α and Ki-67 in tumor tissues was evaluated immunohistochemistry,the results were analyzed by Kruskal-Wallis test and Nemenyi test.The correlation between the expression level of FR-α and cell proliferation index Ki-67 was analyzed by Pearson correlation analysis.Results Western blot analysis showed that the FR-α was not expressed in normal brain tissue and oligodendroglioma tissue,but highly expressed in astrocytoma,oligodendroastrocytoma and gliomablastoma.The expression level in WHO Ⅲ astrocytoma was significantly higher than in WHO Ⅱ (t =4.497,P < 0.05).FR-α was also highly expressed in oligodendroastrocytoma and its expression level in WHO Ⅲ was also significantly higher than in the WHO Ⅱ (t =2.876,P <0.05).Foremore,immunohistochemistry analysis also showed that FR-α was not expressed in oligodendroglioma,but expressed in astrocytoma,oligodendroastrocytoma and gliomablastoma.The positive rate of FR-α of WHO Ⅲ was significantly higher than the WHO Ⅱ astrocytoma (57.8% ± 2.2% vs.45.7% ± 2.3%,x2 =3.871,P =0.034).In oligodendroastrocytoma,the positive rate of FR-α of WHO Ⅲ was significantly higher than the WHO Ⅱ (56.5% ±5.4% vs.37.1% ±5.2%,x2 =4.454,P =0.021).Moreover,the expression level of FR-αt in gliomablastoma was highest in all histological types of gliomas,the positive rate of FR-α was up to 65.0% ± 4.5%.Pearson correlation analysis showed that the positive rate of FR-α was positively correlated with Ki-67 index (r =0.903,P <0.05).Conclusions FR-α is expressed in astrocytoma,oligodendroastrocytoma and glioblastoma,and the expression level of FR-α is positively correlated with malignancy grade and Ki-67 index.Therefore,FR-α may be applied as a special target for diagnosis and treatment of glioma.

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