Research Papers:
Identification of distinct molecular subtypes of uterine carcinosarcoma
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Abstract
Yang An1,2, Haojie Wang1,2, Jingyao Jie1,2, Yitai Tang3, Weijuan Zhang1,2, Shaoping Ji1,2,4, Xiangqian Guo1,2,5,6
1Department of Biochemistry and Molecular Biology, Medical School, Henan University, Kaifeng 475004, China
2Cell Signal Transduction Laboratory, Henan University, Kaifeng 475004, China
3Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA
4Department of Oncology, The First Affiliated Hospital of Henan University, Kaifeng, 475001, China
5Department of Preventive Medicine, Medical School, Henan University, Kaifeng 475004, China
6Department of Burn and Plastic Surgery, The Affiliated Nanshi Hospital of Henan University, Nanyang, 473003, China
Correspondence to:
Xiangqian Guo, email: [email protected]
Shaoping Ji, email: [email protected]
Keywords: uterine carcinosarcoma, molecular subtype, molecular signature, gene expression pattern, subtype-specific treatment
Received: August 11, 2016 Accepted: January 06, 2017 Published: February 02, 2017
ABSTRACT
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.
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