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Identification of metabolism-associated molecular subtype in ovarian cancer |
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| Authors: | Xiaona Liu Aoshen Wu Xing Wang Yunhe Liu Yiang Xu Gang Liu Lei Liu |
| Institution: | 1. Institutes of Biomedical Sciences, Fudan University, Shanghai, China
Contribution: Conceptualization (equal), Formal analysis (equal), Methodology (equal), Writing - original draft (equal);2. Institutes of Biomedical Sciences, Fudan University, Shanghai, China Contribution: Formal analysis (equal), Software (equal), Writing - original draft (equal);3. Institutes of Biomedical Sciences, Fudan University, Shanghai, China Contribution: Conceptualization (equal), Formal analysis (equal), Writing - original draft (equal);4. Institutes of Biomedical Sciences, Fudan University, Shanghai, China Contribution: Methodology (equal);5. School of Basic Medical Sciences, Fudan University, Shanghai, China State Key Laboratory of Neuroscience, Institute of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China University of Chinese Academy of Sciences, Beijing, China Contribution: Investigation (equal);6. Institutes of Biomedical Sciences, Fudan University, Shanghai, China |
| Abstract: | Ovarian cancer (OC) is the most lethal gynaecological cancer with genomic complexity and extensive heterogeneity. This study aimed to characterize the molecular features of OC based on the gene expression profile of 2752 previously characterized metabolism-relevant genes and provide new strategies to improve the clinical status of patients with OC. Finally, three molecular subtypes (C1, C2 and C3) were identified. The C2 subtype displayed the worst prognosis, upregulated immune-cell infiltration status and expression level of immune checkpoint genes, lower burden of copy number gains and losses and suboptimal response to targeted drug bevacizumab. The C1 subtype showed downregulated immune-cell infiltration status and expression level of immune checkpoint genes, the lowest incidence of BRCA mutation and optimal response to targeted drug bevacizumab. The C3 subtype had an intermediate immune status, the highest incidence of BRCA mutation and a secondary optimal response to bevacizumab. Gene signatures of C1 and C2 subtypes with an opposite expression level were mainly enriched in proteolysis and immune-related biological process. The C3 subtype was mainly enriched in the T cell-related biological process. The prognostic and immune status of subtypes were validated in the Gene Expression Omnibus (GEO) dataset, which was predicted with a 45-gene classifier. These findings might improve the understanding of the diversity and therapeutic strategies for OC. |
| Keywords: | immune metabolic genes ovarian cancer prognosis subtype |