An Yang, Wang Haojie, Jie Jingyao, Tang Yitai, Zhang Weijuan, Ji Shaoping, Guo Xiangqian
Department of Biochemistry and Molecular Biology, Medical School, Henan University, Kaifeng 475004, China.
Cell Signal Transduction Laboratory, Henan University, Kaifeng 475004, China.
Oncotarget. 2017 Feb 28;8(9):15878-15886. doi: 10.18632/oncotarget.15032.
Uterine carcinosarcoma (UCS) is a rare but lethal neoplasm with high metastasis and recurrence rate, and to date, no molecular classification of UCS has been defined to achieve targeted therapies. In this study, we identified two distinct molecular subtypes of UCS with distinct gene expression patterns and clinicopathologic characteristics. Subtype I UCS recapitulates low-grade UCS, in contrast subtype II UCS represents high-grade UCS with higher tumor invasion rate and tumor weight. Interestingly, subtype I UCS is characterized by cell adhesion and apoptosis pathways, whereas genes over-expressed in subtype II UCS are more involved in myogenesis/muscle development. We also proposed certain potential subtype specific therapeutic targets, such as SYK (spleen tyrosine kinase) for subtype I and cell-cycle proteins for subtype II. Our findings provide a better recognition of UCS molecular subtypes and subtype specific oncogenesis mechanisms, and can help develop more specific targeted treatment options for these tumors.
子宫癌肉瘤（UCS）是一种罕见但致命的肿瘤，具有高转移率和复发率，迄今为止，尚未定义UCS的分子分类以实现靶向治疗。在本研究中，我们鉴定出两种不同的UCS分子亚型，它们具有不同的基因表达模式和临床病理特征。I型UCS概括了低级别UCS，相比之下，II型UCS代表高级别UCS，具有更高的肿瘤侵袭率和肿瘤重量。有趣的是，I型UCS的特征在于细胞粘附和凋亡途径，而在II型UCS中过表达的基因更多地参与肌生成/肌肉发育。我们还提出了某些潜在的亚型特异性治疗靶点，例如I型的SYK（脾酪氨酸激酶）和II型的细胞周期蛋白。我们的研究结果能更好地认识UCS分子亚型和亚型特异性肿瘤发生机制，并有助于为这些肿瘤开发更具特异性的靶向治疗方案。
