在膀癌中转录因子的性别决定区域Y-box 2 (SOX2)
Rachel L Griffin1, Lauren Shuman2, Hironobu Yamashita2
1Department of Comparative Medicine, Penn State College of Medicine Hershey, PA, USA.
概括
性别决定区域Y-box 2 (SOX2) 是膀癌的一个关键瘤基因. 较高的SOX2表达与晚期瘤阶段相关,并在临床前模型中促进瘤生长和转移.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 尿癌研究 尿癌研究
背景情况:
- 性别决定区域Y-box 2 (SOX2) 是胚胎发育中的一个关键的转录因子.
- 在包括膀癌在内的各种癌症中,SOX2作为瘤基因起作用.
- 以前的研究将SOX2活性与早期膀癌细胞循环失调联系起来.
研究的目的:
- 为了研究SOX2在膀癌中的作用.
- 分析SOX2表达,瘤阶段,临床结果和瘤性之间的关联.
- 评估SOX2对瘤进展和攻击性特征的影响.
主要方法:
- 在303个囊切除样本和25个非侵入性乳头尿路细胞癌样本中使用免疫组织化学的量化SOX2基因表达.
- 通过RNA测序分析SOX2表达在来自公共存储库的非肌肉侵入性和肌肉侵入性膀癌队列中.
- 通过使用MB49-SOX小鼠全移植来评估SOX2的体内瘤性.
主要成果:
- 在40%的非侵入性乳头癌 (IHC) 中检测到SOX2表达,并与RNA测序数据相关 (r=0.6).
- 肌肉侵入性膀癌的SOX2表达明显高于非侵入性类型 (RNA-seq,P<0.001).
- 在小鼠模型中,SOX2表达与膜自身侵袭性癌症 (HR=2,P=0.05) 的阶段进展 (HR=2,P=0.05) 和瘤大小和转移的增加有关.
结论:
- 膀瘤中的焦点SOX2表达可能会驱动瘤发生并促进攻击性特征.
- SOX2与早期膀癌的进展阶段有关.
- 作为膀癌的治疗点,SOX2活性需要进一步研究.
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