Programa de Carcinogênese Molecular, Instituto Nacional de Câncer-INCA, Rua André Cavalcanti, 37 - Centro, Rio de Janeiro, RJ 20231-050, Brazil.
Laboratório de Interações Celulares, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro Prédio de Ciências da Saúde-Cidade Universitária, Ilha do Fundão, A. Carlos Chagas, 373-bloco F, sala 26, Rio de Janeiro, RJ 21941-902, Brasil.
Genes (Basel). 2019 May 15;10(5):372. doi: 10.3390/genes10050372.
Endometrioid endometrial carcinomas (EEC) are the most common malignant gynecologic tumors. Despite the increase in EEC molecular knowledge, the identification of new biomarkers involved in disease's development and/or progression would represent an improvement in its course. High-mobility group A protein (HMGA) family members are frequently overexpressed in a wide range of malignancies, correlating with a poor prognosis. Thus, the aim of this study was to analyze HMGA1 and HMGA2 expression pattern and their potential role as EEC biomarkers. HMGA1 and HMGA2 expression was initially evaluated in a series of 46 EEC tumors (stages IA to IV), and the findings were then validated in The Cancer Genome Atlas (TCGA) EEC cohort, comprising 381 EEC tumors (stages IA to IV). Our results reveal that HMGA1 and HMGA2 mRNA and protein are overexpressed in ECC, but only expression is associated with increased histological grade and tumor size. Moreover, but not overexpression was identified as a negative prognostic factor to EEC patients. Finally, a positive correlation between expression of pseudogenes- and -and HMGA1 itself was detected, suggesting HMGA1 pseudogenes may play a role in HMGA1 expression regulation in EEC. Thus, these results indicate that overexpression possesses a potential role as a prognostic biomarker for EEC.
子宫内膜样型子宫内膜癌(EEC)是最常见的妇科恶性肿瘤。尽管 EEC 的分子知识有所增加,但鉴定参与疾病发展和/或进展的新生物标志物将代表其病程的改善。高迁移率族蛋白 A(HMGA)家族成员在广泛的恶性肿瘤中经常过度表达,与预后不良相关。因此,本研究旨在分析 HMGA1 和 HMGA2 的表达模式及其作为 EEC 生物标志物的潜在作用。最初在 46 例 EEC 肿瘤(IA 期至 IV 期)系列中评估了 HMGA1 和 HMGA2 的表达,然后在包含 381 例 EEC 肿瘤(IA 期至 IV 期)的癌症基因组图谱(TCGA)EEC 队列中验证了这些发现。我们的研究结果表明,HMGA1 和 HMGA2 mRNA 和蛋白在 ECC 中过度表达,但只有 表达与组织学分级和肿瘤大小增加相关。此外,只有 过表达被确定为 EEC 患者的预后不良因素。最后,还检测到 HMGA1 假基因-和 -与 HMGA1 本身表达之间存在正相关,这表明 HMGA1 假基因可能在 EEC 中 HMGA1 表达调控中发挥作用。因此,这些结果表明 过表达可能作为 EEC 的预后生物标志物发挥作用。
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