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糖基磷脂酰肌醇锚定蛋白(GPI-80)基因表达与人胸腺瘤分期相关。

Glycosylphosphatidyl inositol-anchored protein (GPI-80) gene expression is correlated with human thymoma stage.

作者信息

Sasaki Hidefumi, Ide Nobuyuki, Sendo Fujiro, Takeda Yuji, Adachi Masakazu, Fukai Ichiro, Fujii Yoshitaka

机构信息

Department of Surgery II, Nagoya City University Medical School, Mizuho-ku, Nagoya 467-8601, Japan.

出版信息

Cancer Sci. 2003 Sep;94(9):809-13. doi: 10.1111/j.1349-7006.2003.tb01523.x.

Abstract

Thymoma is one of the most common solid tumors in the mediastinum. Because there is no typical cell line for human thymoma, the development and use of molecular-based therapy for thymoma will require detailed molecular-genetic analysis of patients' tissues. Recent reports showed that genetic aberrations in thymoma were most frequently seen in chromosome 6q regions. We investigated the use of oligonucleotide arrays to monitor in vivo expression levels of genes in chromosome 6 regions in early- (stage I or II) and late- (stage IVa) stage thymoma tissues from patients. These in vivo gene expression profiles were verified by real-time quantitative reverse transcription polymerase chain reaction (RT-PCR) using LightCycler for 48 thymoma patients and sandwich ELISA for 33 thymoma patients. Using both methods, a candidate gene was identified which was overexpressed in stage IV thymoma. This was a known glycosylphosphatidyl inositol (GPI)-anchored protein (GPI-80), which is highly homologous with Vanin-1, a mouse thymus homing protein. Serum level of GPI-80 was confirmed to be elevated in stage IV thymoma compared with in stage I thymoma by using sandwich ELISA. The combined use of oligonucleotide microarray, real-time RT-PCR, and ELISA analyses provides a powerful new approach to elucidate the in vivo molecular events surrounding the development and progression of thymoma.

摘要

胸腺瘤是纵隔最常见的实体瘤之一。由于人类胸腺瘤没有典型的细胞系,因此胸腺瘤分子靶向治疗的开发和应用需要对患者组织进行详细的分子遗传学分析。最近的报告显示,胸腺瘤中的基因畸变最常见于6号染色体q区域。我们研究了使用寡核苷酸阵列监测患者早期(I期或II期)和晚期(IVa期)胸腺瘤组织中6号染色体区域基因的体内表达水平。这些体内基因表达谱通过实时定量逆转录聚合酶链反应(RT-PCR)进行验证,其中48例胸腺瘤患者使用LightCycler,33例胸腺瘤患者使用夹心ELISA。使用这两种方法,鉴定出一个在IV期胸腺瘤中过表达的候选基因。这是一种已知的糖基磷脂酰肌醇(GPI)锚定蛋白(GPI-80),它与小鼠胸腺归巢蛋白Vanin-1高度同源。通过夹心ELISA证实,与I期胸腺瘤相比,IV期胸腺瘤患者血清中GPI-80水平升高。寡核苷酸微阵列、实时RT-PCR和ELISA分析的联合应用为阐明胸腺瘤发生和发展过程中的体内分子事件提供了一种强大的新方法。

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