色素上皮衍生因子在神经母细胞肿瘤中的表达及促分化作用的研究

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目的观察色素上皮衍生因子(PEDF)在神经母细胞肿瘤中的表达情况及在分化中的作用。方法采用免疫组织化学方法对23例神经母细胞瘤(NB)、17例节细胞神经母细胞瘤(GNB)、18例节细胞神经瘤(GN)的标本进行PEDF免疫染色分析,每张切片采用显微数字分析系统进行定量,统计指标为免疫染色评分(immunostaining score,ISS),ISS=阳性染色面积×阳性染色面积的平均光密度/整个视野面积。进一步采用Western印迹对4例NB、3例GNB进行PEDF定量分析,以β-actin为内参照,统计指标为PEDF/Actin比值。NB、GNB和GN中PEDF表达差异性的比较采用KruskaI-Wallis法和Nemenyi法检验;采用Spearman等级相关进行PEDF表达强度与神经母细胞肿瘤成熟程度相关性分析。NB和GNB中的PEDF/β-actin比值比较采用t检验。结果免疫组织化学显示随着NB向GNB发育过程中,PEDF的表达量逐渐增加(P=0.000),PEDF的表达强度与神经母细胞肿瘤的成熟程度呈正相关(r_s=0.889,P=0.000)。GNB中PEDF/Actin的比值较NB中高(P=0.045)。结论PEDF可能为神经母细胞肿瘤内源性促分化因子.诱导原始神经母细胞向成熟的节细胞分化,可应用于消灭微小残留灶的维持治疗中,前景令人鼓舞。 Objective To observe the expression of pigment epithelium-derived factor (PEDF) in neuroblastoma and its role in differentiation. Methods 23 cases of neuroblastoma (NB), 17 cases of ganglioneuroblastoma (GNB) and 18 cases of ganglioneuroma (GN) were immunohistochemically analyzed by PEDF immunostaining. Each section was The microscopic digital analysis system was used for quantification. The statistical indicators were immunostaining score (ISS), ISS = positive staining area × average optical density of positive staining area / total field of view. Western blotting was used to analyze the PEDF in 4 cases of NB and 3 cases of GNB. Β-actin was taken as internal reference, and the statistical index was PEDF / Actin ratio. The difference of PEDF expression in NB, GNB and GN was tested by KruskaI-Wallis method and Nemenyi method. Spearman rank correlation was used to analyze the correlation between PEDF expression intensity and neuroblastoma tumor maturation. The t-test was used to compare the PEDF / β-actin ratios in NB and GNB. Results Immunohistochemistry showed that the expression of PEDF increased with the development of GNB (P = 0.000). The expression of PEDF was positively correlated with the maturation of neuroblastoma (r_s = 0.889, P = 0.000). The ratio of PEDF / Actin in GNB was higher than in NB (P = 0.045). Conclusions PEDF may be the endogenous pro-differentiation factor of neuroblastoma, and the induction of primitive neuroblastoma into mature section cells can be applied in the maintenance therapy of eliminating minimal residual tumor. The prospect is encouraging.
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