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MAPK7 和 MAP2K4 作为骨肉瘤的预后标志物。

MAPK7 and MAP2K4 as prognostic markers in osteosarcoma.

机构信息

Department of Pediatrics, Pediatric Oncology Institute (Grupo de Apoio ao Adolescente e à Criança com Câncer), Federal University of São Paulo, São Paulo, SP 04023-062, Brazil.

出版信息

Hum Pathol. 2012 Jul;43(7):994-1002. doi: 10.1016/j.humpath.2011.08.003. Epub 2011 Dec 9.

Abstract

Osteosarcoma is a class of cancer originating from the bone, affecting mainly children and young adults. Cytogenetic studies showed the presence of rearrangements and recurrent gains in specific chromosomal regions, indicating the possible involvement of genes located in these regions during the pathogenesis of osteosarcoma. These studies investigated expression of 10 genes located in the chromosomal region involved in abnormalities in osteosarcoma, 1p36, 17p, and chromosome 19. The purpose of this study was to investigate the expression profile of genes located in regions involved in chromosomal rearrangements in osteosarcoma. We used quantitative real-time polymerase chain reaction to investigate the expression of 10 genes located in 1p36.3 (MTHFR, ERRFI1, FGR, E2F2), 17p (MAPK7, MAP2K4), and chromosome 19 (BBC3, FOSB, JUND, and RRAS), in 70 samples taken from 30 patients (30 prechemotherapy, 30 postchemotherapy, and 10 metastases specimens) and 10 healthy bones as a control sample. The most interesting results showed a strong association between the expression levels of MAPK7 and MAP2K4 genes and clinical parameters of osteosarcoma. Overexpression of these genes was significantly associated to a poor response to treatment (P = .0001 and P = .0049, respectively), tumor progression, and worse overall survival (P = .0052 and P = .0085, respectively), suggesting that MAPK7 and MAP2K4 could play an important role in osteosarcoma tumorigenesis. Thus, these genes could be good markers in assessing response to treatment and development of osteosarcoma.

摘要

骨肉瘤是一种起源于骨骼的癌症,主要影响儿童和青少年。细胞遗传学研究表明,特定染色体区域存在重排和反复增益,表明这些区域的基因可能参与骨肉瘤的发病机制。这些研究调查了位于骨肉瘤异常相关染色体区域的 10 个基因的表达,这些基因位于 1p36、17p 和 19 号染色体上。本研究旨在探讨位于染色体重排相关区域的基因在骨肉瘤中的表达谱。我们使用定量实时聚合酶链反应(PCR)技术检测了 70 个样本(30 个化疗前、30 个化疗后和 10 个转移标本)和 10 个健康骨组织中 10 个基因(位于 1p36.3 的 MTHFR、ERRFI1、FGR、E2F2,位于 17p 的 MAPK7、MAP2K4,以及位于 19 号染色体的 BBC3、FOSB、JUND 和 RRAS)的表达。最有趣的结果显示,MAPK7 和 MAP2K4 基因的表达水平与骨肉瘤的临床参数之间存在很强的相关性。这些基因的过表达与对治疗的反应不良(P =.0001 和 P =.0049)、肿瘤进展和总体生存率降低显著相关(P =.0052 和 P =.0085),表明 MAPK7 和 MAP2K4 可能在骨肉瘤的发生中发挥重要作用。因此,这些基因可能是评估治疗反应和骨肉瘤发生的良好标志物。

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