Distinct molecular subtypes of uterine leiomyosarcoma respond differently to chemotherapy treatment

• Main Authors: Yang An, Shuzhen Wang, Songlin Li, Lulu Zhang, Dayong Wang, Haojie Wang, Shibai Zhu, Wan Zhu, Yongqiang Li, Wenwu Chen, Shaoping Ji, Xiangqian Guo
• Format: Article
• Language: English
• Published: BMC 2017-09-01
• Series: BMC Cancer
• Subjects: Uterine leiomyosarcoma; Molecular subtype; Molecular signature; Gene expression pattern; Subtype-specific treatment
• Online Access: http://link.springer.com/article/10.1186/s12885-017-3568-y

Abstract Background Uterine leiomyosarcoma (ULMS) is an aggressive form of soft tissue tumors. The molecular heterogeneity and pathogenesis of ULMS are not well understood. Methods 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. Results 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. Conclusions 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.