Cuproptosis-related genes signature could predict prognosis and the response of immunotherapy in cervical cancer

铜凋亡相关基因特征可预测宫颈癌的预后和免疫治疗反应

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Abstract

BACKGROUND: A lot of studies have shown a close relationship between cuproptosis and cancer. The main purpose of this study is to analyze the impact of cuproptosis on cervical cancer (CC). METHODS: Using The Cancer Genome Atlas (TCGA) public database, we analyzed the genetic correlation, expression, and prognostic value of 25 cuproptosis-related genes (CRGs) in CC. A least absolute shrinkage and selection operator (LASSO) risk regression model was constructed to compare the changes in associated pathways, prognosis, immune infiltration, and antibody programmed cell death-ligand 1 (anti-PD-L1) treatment response of the high- and low-risk groups. In addition, we collected CC tissue samples before and after radiotherapy for ribonucleic acid (RNA) sequencing, and analyzed the relationship between CRGs and radiotherapy. RESULTS: The results showed CRGs were differentially expressed and were associated with multiple metabolic pathways. High expression of COX7B, PIH1D2, NDUFA1, NDUFA2 and NDUFB1 indicated a better prognosis. CRGs signature could predict prognosis (P<0.001) and affect immune infiltration. The prognosis was better in the low-risk group, while the high-risk group was more correlated with PD-L1. SLC25A5 downregulated expression (P=0.001) and SLC6A3 upregulated (P=0.02) after radiotherapy. SLC25A5 was related to the degree of differentiation of CC; the worse the differentiation, the higher the expression. CONCLUSIONS: CRGs may further affect patient prognosis and response to immunotherapy by influencing metabolic pathways and immune infiltration. Radiation could alter the expression of CRGs, which may have potential research value in evaluating the efficacy of radiotherapy.

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