铜死亡相关关键基因在卵巢癌中的作用及预后模型的构建^*

The Role of Cuproptosis Related Key Genes in Ovarian Cancer and the Construction of a Prognostic Model

摘要

目的 利用公共数据库中的卵巢癌数据集，确定卵巢癌组织中的铜死亡相关基因，并基于这些基因构建卵巢癌患者临床预后风险评分模型。方法 从TCGA OC数据库和GEO数据库中的GSE26193、GSE63885数据集，筛选出10个铜死亡相关基因，并基于数据集分析其染色体定位、表达相关性和突变模式。基于这些基因，我们对卵巢癌样本进行聚类，以识别铜诱导死亡的不同分子亚型。分析不同亚型之间的差异表达基因和功能富集，并通过生存回归分析获得了具有预后预测能力的特征基因。基于这些特征基因，我们构建了一个风险评分模型，并结合患者的临床特征，共同预测其生存率。结果 在卵巢癌样本中，10个铜死亡相关基因可将样本稳定区分为两种分子亚型，二者临床及免疫特征、药物敏感性等方面差异明显。进一步筛选获得7个预后基因（RARRES1、CXCL10、PI3、CXCL11、THEMIS2、GBP2、RPL39L），基于其建立的风险模型结合年龄后对患者1、3、5年生存率预测的曲线下面积均大于0.7，显示良好临床应用前景。结论 铜死亡的机制及其关键基因可能成为卵巢癌的治疗靶点。该分型为临床个体化治疗提供了理论依据。由关键预后基因构建的预测模型具有良好的临床应用效果。

Abstract

Objective Using ovarian cancer datasets from public databases, identify copper death-related genes in ovarian cancer tissues and construct a clinical prognostic risk scoring model for ovarian cancer patients based on these genes. Methods We downloaded the OC data of TCGA, the GSE26193, GSE63885 dataset from GEO and retrieved 10 cuproptosis related genes (CRGs) and analyzed their chromosomal localization, expression correlation, and mutation patterns based on the datasets. Using these genes, we clustered the OC samples to identify different molecular subtypes of copper induced death. We analyzed the differential genes and functional enrichment between different subtypes and obtained feature genes with predictive ability for prognosis through survival regression analyses. Based on these feature genes, we constructed a risk scoring model and incorporated the clinical characteristics of patients to jointly predict their survival rate. Results In ovarian cancer samples, 10 copper death-related genes can stably divide the samples into two molecular subtypes, and there are significant differences in clinical and immune characteristics and drug sensitivity between them. After further screening, seven prognostic genes (RARRES1, CXCL10, PI3, CXCL11, THEMIS2, GBP2, RPL39L) were obtained, and the risk model based on them combined with age predicted that the AUC of patients' 1-, 3-, and 5-year survival rates were all greater than 0.7, showing good clinical application prospects. Conclusion The mechanism of cuproptosis and its key genes might become therapeutic targets for ovarian cancer. The subtypes of cuproptosis provide a theoretical basis for personalized clinical treatment. The predictive model constructed by key prognostic genes has promising clinical application effects.

关键词

卵巢癌 / 铜死亡相关基因 / 免疫浸润

Key words

Ovarian cancer / Cuproptosis-related genes / Immune infiltration

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基金资助

*辽宁省科技计划联合计划（自然科学基金-面上项目）(2024-MSLH-275)

卫生健康发展促进项目（肿瘤科研专项）(KC2023-JX-0186-RQ068)