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G 蛋白偶联受体 5D 在骨髓中的过表达与多发性骨髓瘤患者的预后不良相关。

Overexpression of G protein-coupled receptor 5D in the bone marrow is associated with poor prognosis in patients with multiple myeloma.

机构信息

Department of Medicine I, Division of Hematology and Hemostaseology, Medical University Vienna, Austria.

出版信息

Eur J Clin Invest. 2012 Sep;42(9):953-60. doi: 10.1111/j.1365-2362.2012.02679.x. Epub 2012 May 16.

Abstract

BACKGROUND

G protein-coupled receptor 5D (GPRC5D) is a novel surface receptor. As this new subtype of G protein-coupled receptors was discovered, little is known about the role of this gene.

MATERIALS AND METHODS

In this retrospective study, we investigated GPRC5D mRNA expression by real-time polymerase chain reaction (RT-PCR) in bone marrow (BM) of 48 patients with multiple myeloma (MM).

RESULTS

Highly variable levels of GPRC5D (median, 288; quartiles, 17-928) were detected in patients with MM, whereas only low expression was detected in normal tissues (median, 1; quartiles, 1-23). High mRNA expression of GPRC5D correlated positively with high plasma cell count in bone marrow (r = 0·64, P < 0·001), high β(2) -microglobulin (r = 0·42, P = 0·003) and poor-risk cytogenetics: deletion 13q14 (rb-1), P = 0·003; and 14q32 translocation t(4;14)(p16;q32), P = 0·029. GPRC5D mRNA expression showed a significant correlation with overall survival (P = 0·031). The estimated overall survival of patients expressing GPRC5D above or below the median of 288 was 43·9% vs. 70·2% at 48 months. Here, we report, for the first time, the association of GPRC5D expression and cancer.

CONCLUSIONS

Overexpression in poor-risk myeloma, low expression in normal tissues and cell surface expression identify GPRC5D as a potential novel cancer antigen. Our data demonstrate that GPRC5D is a prognostic factor in MM correlating with other major risk factors.

摘要

背景

G 蛋白偶联受体 5D(GPRC5D)是一种新型的表面受体。随着这种新型 G 蛋白偶联受体亚型的发现,人们对该基因的作用知之甚少。

材料和方法

在这项回顾性研究中,我们通过实时聚合酶链反应(RT-PCR)检测了 48 例多发性骨髓瘤(MM)患者骨髓(BM)中的 GPRC5D mRNA 表达。

结果

在 MM 患者中检测到高度可变的 GPRC5D 水平(中位数为 288;四分位距为 17-928),而在正常组织中仅检测到低表达(中位数为 1;四分位距为 1-23)。GPRC5D 的高 mRNA 表达与骨髓中浆细胞计数高(r = 0.64,P < 0.001)、β(2)-微球蛋白高(r = 0.42,P = 0.003)和不良细胞遗传学相关:13q14 缺失(rb-1),P = 0.003;和 14q32 易位 t(4;14)(p16;q32),P = 0.029。GPRC5D mRNA 表达与总生存显著相关(P = 0.031)。表达 GPRC5D 高于或低于中位数 288 的患者的估计总生存率分别为 43.9%和 70.2%,在 48 个月时。在这里,我们首次报告了 GPRC5D 表达与癌症的关联。

结论

在不良风险的骨髓瘤中过度表达,在正常组织中低表达,以及在细胞表面表达,将 GPRC5D 鉴定为一种潜在的新型癌症抗原。我们的数据表明,GPRC5D 是 MM 的预后因素,与其他主要危险因素相关。

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