Distinct molecular subtypes of uterine leiomyosarcoma respond differently to chemotherapy treatment
Yang An,
Shuzhen Wang,
Songlin Li,
Lulu Zhang,
Dayong Wang,
Haojie Wang,
Shibai Zhu,
Wan Zhu,
Yongqiang Li,
Wenwu Chen,
Shaoping Ji,
Xiangqian Guo
Affiliations
Yang An
Department of Biochemistry and Molecular Biology, Joint National Laboratory for Antibody Drug Engineering, Institute of Biomedical Informatics, Medical School, Henan University
Shuzhen Wang
Department of Biochemistry and Molecular Biology, Joint National Laboratory for Antibody Drug Engineering, Institute of Biomedical Informatics, Medical School, Henan University
Songlin Li
Department of Biochemistry and Molecular Biology, Joint National Laboratory for Antibody Drug Engineering, Institute of Biomedical Informatics, Medical School, Henan University
Lulu Zhang
Department of Biochemistry and Molecular Biology, Joint National Laboratory for Antibody Drug Engineering, Institute of Biomedical Informatics, Medical School, Henan University
Dayong Wang
Department of Nuclear Medicine, The First Affiliated Hospital of Henan University
Haojie Wang
Department of Biochemistry and Molecular Biology, Joint National Laboratory for Antibody Drug Engineering, Institute of Biomedical Informatics, Medical School, Henan University
Shibai Zhu
Department of Orthopedic Surgery, Peking Union Medical College, Chinese Academy of Medical Science
Wan Zhu
Department of Anesthesia and Perioperative Care, University of California
Yongqiang Li
Department of Biochemistry and Molecular Biology, Joint National Laboratory for Antibody Drug Engineering, Institute of Biomedical Informatics, Medical School, Henan University
Wenwu Chen
Department of Neurology, The First Affiliated Hospital of Henan University
Shaoping Ji
Department of Biochemistry and Molecular Biology, Joint National Laboratory for Antibody Drug Engineering, Institute of Biomedical Informatics, Medical School, Henan University
Xiangqian Guo
Department of Biochemistry and Molecular Biology, Joint National Laboratory for Antibody Drug Engineering, Institute of Biomedical Informatics, Medical School, Henan University
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.
