Department of Biochemistry and Molecular Biology, Joint National Laboratory for Antibody Drug Engineering, Institute of Biomedical Informatics, Medical School, Henan University, Kaifeng, 475004, China.
Cell signal transduction Laboratory, Henan University, Kaifeng, 475004, China.
BMC Cancer. 2017 Sep 11;17(1):639. doi: 10.1186/s12885-017-3568-y.
Uterine leiomyosarcoma (ULMS) is an aggressive form of soft tissue tumors. The molecular heterogeneity and pathogenesis of ULMS are not well understood.
Expression profiling data were used to determine the possibility and optimal number of ULMS molecular subtypes. Next, clinicopathological characters and molecular pathways were analyzed in each subtype to prospect the clinical applications and progression mechanisms of ULMS.
Two distinct molecular subtypes of ULMS were defined based on different gene expression signatures. Subtype I ULMS recapitulated low-grade ULMS, the gene expression pattern of which resembled normal smooth muscle cells, characterized by overexpression of smooth muscle function genes such as LMOD1, SLMAP, MYLK, MYH11. In contrast, subtype II ULMS recapitulated high-grade ULMS with higher tumor weight and invasion rate, and was characterized by overexpression of genes involved in the pathway of epithelial to mesenchymal transition and tumorigenesis, such as CDK6, MAPK13 and HOXA1.
We identified two distinct molecular subtypes of ULMS responding differently to chemotherapy treatment. Our findings provide a better understanding of ULMS intrinsic molecular subtypes, and will potentially facilitate the development of subtype-specific diagnosis biomarkers and therapy strategies for these tumors.
子宫平滑肌肉瘤（ULMS）是一种侵袭性软组织肿瘤。ULMS 的分子异质性和发病机制尚未完全清楚。
利用表达谱数据确定 ULMS 分子亚型的可能性和最佳数量。然后，分析每个亚型的临床病理特征和分子途径，以预测 ULMS 的临床应用和进展机制。
根据不同的基因表达特征，定义了两种不同的 ULMS 分子亚型。I 型 ULMS 重现了低级别 ULMS，其基因表达模式类似于正常平滑肌细胞，特征是平滑肌功能基因如 LMOD1、SLMAP、MYLK 和 MYH11 的过度表达。相比之下，II 型 ULMS 重现了高级别 ULMS，其肿瘤重量和侵袭率更高，其特征是参与上皮间质转化和肿瘤发生途径的基因如 CDK6、MAPK13 和 HOXA1 的过度表达。
我们确定了两种不同的 ULMS 分子亚型，它们对化疗治疗的反应不同。我们的发现为 ULMS 内在分子亚型提供了更好的理解，并可能有助于开发这些肿瘤的亚型特异性诊断生物标志物和治疗策略。
