STC2 overexpression mediated by HMGA2 is a biomarker for aggressiveness of high-grade serous ovarian cancer
STC2 overexpression mediated by HMGA2 is a biomarker for aggressiveness of high-grade serous ovarian cancer
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HMGA2 介导的 STC2 过表达是高级别浆液性卵巢癌侵袭性的生物标志物
DOI：
10.3892/or.2015.4120
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发表时间：
2015-09-01
期刊：
影响因子：
4.2
通讯作者：
Wei, Jian-Jun
中科院分区：
文献类型：
--
作者：
Wu, Jingjing;Lai, Maode;Wei, Jian-Jun
高级别浆液性癌（HGSC）是由于浸润和早期转移而导致的卵巢癌的致命形式。上皮-间质转化（EMT）的获得有助于HGSC的侵袭性。高迁移率基因组A2（HMGA 2）是一种结构性转录因子，通过调控EMT基因表达在HGSC中发挥重要作用。基于基因表达谱分析，我们发现有效的EMT基因斯钙素2（STC 2）与HMGA 2表达高度相关。在本研究中，我们证明了STC 2在转录水平上直接受HMGA 2的调控。在体外过表达STC 2直接增强细胞迁移和侵袭。为了研究STC 2和HMGA 2表达与卵巢癌的潜在生物标志物的相关性，在本研究中检查了三个独立的大型卵巢癌队列（队列1=278，队列2=150和队列3=95例）。结果显示HMGA 2和STC 2的表达呈正相关。此外，STC 2表达与肿瘤分级和组织类型显著相关。HGSC具有显著更高水平的STC 2表达，并且与患者存活率呈负相关。这些发现表明，STC 2是一个重要的新的生物标志物，可用于HGSC。
High-grade serous cancer (HGSC) is a lethal form of ovarian cancer due to invasion and early metastasis. Gain of epithelial-mesenchymal transition (EMT) contributes to the aggressiveness of HGSC. High-mobility gene group A2 (HMGA2), an architectural transcription factor, plays a major role in HGSC through the regulation of EMT gene expression. Based on the gene profiling analysis, we found that the potent EMT gene, stanniocalcin 2 (STC2), was highly correlated with HMGA2 expression. In the present study, we demonstrated that STC2 was directly regulated by HMGA2 at the transcriptional level. Overexpressing STC2 in vitro directly enhanced cell migration and invasion. To investigate the correlation of STC2 and HMGA2 expression and the potential biomarker for ovarian cancer, three independent large cohorts of ovarian cancer (cohort 1=278, cohort 2=150 and cohort 3=95 cases) were examined in the present study. The results showed that the expression of HMGA2 and STC2 was positively correlated. Furthermore, STC2 expression was significantly associated with tumor grade and histotype. HGSC had significantly higher levels of STC2 expression and was inversely correlated with patient survival. These findings suggested that STC2 is an important new biomarker that can be used for HGSC.