Digital Polymerase Chain Reaction Quantification of SERPINA1 Predicts Prognosis in High-Grade Glioma

Digital Polymerase Chain Reaction Quantification of SERPINA1 Predicts Prognosis in High-Grade Glioma
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DOI:
10.1016/j.wneu.2017.12.166
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发表时间:
2018-03-01
期刊:
影响因子:
2
通讯作者:
Honmou, Osamu
Honmou, Osamu
中科院分区:
医学4区
文献类型:
--
作者:
Ookawa, Satoshi;Wanibuchi, Masahiko;Honmou, Osamu

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背景:SERPINA 1在保护组织免受蛋白水解机制的影响中发挥抗炎作用。免疫组化分析显示SERPINA 1在胶质瘤中呈阳性,然而,SERPINA 1的作用,包括与预后的关系,一直不确定。近年来,数字聚合酶链反应(digital polymerase chain reaction,PCR)已成为检测福尔马林固定石蜡包埋(formalin-fixed paraffin-embedded,FFPE)组织中信使RNA表达的一种超灵敏的方法。目的:本研究应用数字聚合酶链反应(digital PCR)定量检测高级别胶质瘤(high-grade glioma,HGG)中SERPINA 1的表达,并分析其与预后的关系。来自HGG患者的29份FFPE手术样本(7份为世界卫生组织[WHO] III级,22份为WHO IV级)和人胶质母细胞瘤细胞系U87和U118用于分析。结果:免疫组化染色结果显示SERPINA 1在胶质瘤组织和多形性胶质母细胞瘤细胞系中均有表达。数字PCR分析显示,SERPINA 1在III级和IV级HGG患者的组织中的表达率分别为14.3%和63.6%(P = 0.035)。SERPINA 1低表达组的中位生存期为38.8个月,高于高表达组的15.3个月(P = 0.030)。SERPINA 1的高表达提示HGG预后不良。
BACKGROUND: SERPINA1 plays an anti-inflammatory role in protecting tissues from proteolytic mechanisms. SERPINA1 is positive in gliomas by immunohistochemical analysis; however, the role of SERPINA1, including the relationship with prognosis, has been uncertain. In recent years, digital polymerase chain reaction (PCR) has provided ultra-sensitive assessment of messenger RNA expression from formalin-fixed paraffin-embedded (FFPE) tissues.OBJECTIVE: In this study, we quantitatively determined the expression of SERPINA1 in high-grade gliomas (HGGs) using digital PCR, and we analyzed its relationship with prognosis.METHODS: Twenty-nine FFPE surgical samples from patients with HGGs (7 of World Health Organization [WHO] grade III and 22 of WHO grade IV), and human glioblastoma cell lines, U87 and U118, were used for analysis. A qualitative assessment using immunostaining and quantitative assessment using digital PCR were performed to assess the expression of SERPINA1.RESULTS: The expression of SERPINA1 was demonstrated in glioma tissues and glioblastoma multiforme cell lines by immunostaining. Digital PCR analysis showed that SERPINA1 was expressed in 14.3% and 63.6% of the tissues from patients with grade III and grade IV HGG, respectively (P = 0.035). The median overall survival of 38.8 months in the low SERPINA1 expression group was longer than that of 15.3 months in the high expression group (P = 0.030).CONCLUSIONS: The frequency and the amount of SERPINA1 expression were higher in grade IV than in grade III HGGs. The high expression of SERPINA1 indicates a poor prognosis of HGGs.