Molecular subtypes based on cuproptosis-related genes and tumor microenvironment infiltration characterization in ovarian cancer

基于杯状凋亡相关基因的卵巢癌分子亚型及肿瘤微环境浸润特征

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作者:Jingjing Zhang, Miao Lu, Haoya Xu, Fang Ren, Liancheng Zhu

Background

Cuproptosis (copper death) is a recently found cell death type produced by copper iron; nonetheless, the properties of cuproptosis molecular subtypes and possible involvement of cuproptosis-related genes (CRGs) in the tumor microenvironment (TME) in ovarian cancer (OC) remain unknown.

Conclusions

Our comprehensive analysis of CRGs in OC showed their potential role in TME, clinicopathological characteristics, chemotherapy and targeted drug screening and prognosis. These discoveries could help us better understand CRGs in OC, as well as pave the path for novel ways to assess prognosis and design more effective immunotherapy strategies.

Methods

CRG changes were characterized at the genomic and transcriptional levels in 656 OC samples, and their expression patterns were investigated using three different datasets.

Results

We identified three distinct molecular subtypes, and discovered that variations in molecular subtypes were linked to patient prognosis, TME cell infiltration characteristics, malignancy, and immune-related pathways. Then, in order to predict overall survival (OS), we created a risk score and tested its predictive potential in OC patients. As a result, we created a very accurate nomogram to increase risk score clinical applicability. Better OS, younger age, early stage, and immune activity were all associated with a low risk score. The hallmarks of a high-risk score are older age, advanced stage, immunosuppression, and a bad prognosis. Furthermore, risk score was linked to immune checkpoint expression (including PD-L1, CTLA4), targeted therapy gene expression (PARP, PDGFRA), cancer stem cell (CSC), chemotherapy and targeted medication sensitivity. Conclusions: Our comprehensive analysis of CRGs in OC showed their potential role in TME, clinicopathological characteristics, chemotherapy and targeted drug screening and prognosis. These discoveries could help us better understand CRGs in OC, as well as pave the path for novel ways to assess prognosis and design more effective immunotherapy strategies.

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