Wu Shuaishuai, Ballah Augustine K, Che Wenqiang, Wang Xiangyu
First Affiliated Hospital, Department of Neurosurgery, Jinan University, Guangzhou, China.
J Mol Neurosci. 2023 Mar;73(2-3):185-204. doi: 10.1007/s12031-023-02102-5. Epub 2023 Jan 27.
Cuprotosis is a novel and different cell death mechanism from the existing known ones that can be used to explore new approaches to treating cancer. Just like ferroptosis and pyroptosis, cuprotosis-related genes regulate various types of tumorigenesis, invasion, and metastasis. However, the relationship between cuprotosis-related long non-coding RNA (cuprotosis-related lncRNA) in glioma development and prognosis has not been investigated. We obtained relevant data from the Genotype-Tissue Expression (GTEx), Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA), and published articles. First, we identified 365 cuprotosis-related lncRNAs based on 10 cuprotosis-related differential genes (|R|> 0.4, p < 0.001). Then using Lasso and Cox regression analysis methods, 12 prognostic cuprotosis-related lncRNAs were obtained and constructed the CuLncSigi risk score formula. Our next step was to divide the tumor gliomas into two groups (high risk and low risk) based on the median risk score, and we found that patients in the high-risk group had a significantly worse prognosis. We used internal and external validation methods to simultaneously analyze and validate that the risk score model has good predictive power for patients with glioma. Next, we also performed enrichment analyses such as GSEA and aaGSEA and evaluated the relationship between immune-related drugs and tumor treatment. In conclusion, we successfully constructed a formula of cuprotosis-related lncRNAs with a powerful predictive function. More importantly, our study paves the way for exploring cuprotosis mechanisms in glioma occurrence and development and helps to find new relevant biomarkers for glioma early identification and diagnosis and to investigate new therapeutic approaches.
铜死亡是一种与现有已知机制不同的新型细胞死亡机制,可用于探索治疗癌症的新方法。与铁死亡和焦亡一样,铜死亡相关基因调节各种类型的肿瘤发生、侵袭和转移。然而,铜死亡相关长链非编码RNA(铜死亡相关lncRNA)在胶质瘤发生发展和预后中的关系尚未得到研究。我们从基因型-组织表达(GTEx)、癌症基因组图谱(TCGA)、中国胶质瘤基因组图谱(CGGA)以及已发表的文章中获取了相关数据。首先,我们基于10个铜死亡相关差异基因(|R|> 0.4,p < 0.001)鉴定出365个铜死亡相关lncRNA。然后使用套索回归和Cox回归分析方法,获得了12个与预后相关的铜死亡lncRNA,并构建了CuLncSigi风险评分公式。我们的下一步是根据中位风险评分将肿瘤胶质瘤分为两组(高风险和低风险),我们发现高风险组患者的预后明显更差。我们使用内部和外部验证方法同时分析和验证风险评分模型对胶质瘤患者具有良好的预测能力。接下来,我们还进行了GSEA和aaGSEA等富集分析,并评估了免疫相关药物与肿瘤治疗之间的关系。总之,我们成功构建了一个具有强大预测功能的铜死亡相关lncRNA公式。更重要的是,我们的研究为探索铜死亡在胶质瘤发生发展中的机制铺平了道路,并有助于找到用于胶质瘤早期识别和诊断的新相关生物标志物以及研究新的治疗方法。