Xu Rong, Wu Xin, Du Ashuai, Zhao Qiangqiang, Huang He
NHC Key Laboratory of Carcinogenesis, Cancer Research Institute and School of Basic Medicine, Central South University Changsha 410078, Hunan, China.
Department of Histology and Embryology, Xiangya School of Medicine, Central South University Changsha 410013, Hunan, China.
Am J Cancer Res. 2022 Nov 15;12(11):5241-5254. eCollection 2022.
Cuproptosis is a novel type of cell death that may play a vital role in preventing various types of cancer. Studies examining cuproptosis are limited, and the cuproptosis-related lncRNAs (long non-Coding ribonucleic acids) involved in the regulation of colon cancer remain unclear. This study aimed to identify the prognostic signature of cupronosis-related lncRNAs and explore their potential molecular functions in colon cancer. Data on the clinical correlation were obtained from The Cancer Genome Atlas (TCGA) database. The differentially expressed cuproptosis-related long non-coding ribonucleic acids (lncRNAs) were analyzed using the "limma" package. Then, the prognostic cuproptosis-related lncRNA signature (CupRLSig) was identified through univariate Cox and co-expression analyses, and a prognostic model was constructed based on CupRLSig using the least absolute shrinkage selection operator (LASSO) algorithm and Cox regression analysis. The Kaplan-Meier survival curve and receiver operating characteristic (ROC) curve were used for evaluating the model's capacity for prognosis prediction. In addition, the immune landscape, and drug sensitivity of CupRLSig were analyzed. Finally, the functions of AL512306.3 and ZEB1-AS1 were verified through in vitro experiments. The high- or low-risk groups were classified according to the risk score. The signature-based risk score showed a stronger ability to predict patient's survival compared with the traditional clinicopathological features. In addition, immune responses, such as inflammation-promoting response and T-cell co-inhibition, were significantly different between the two groups. Moreover, chemotherapy drugs or inhibitors, such as axitinib, cisplatin, doxorubicin, and elesclomol, may be considered as potential therapeutic drugs for patients in high-risk groups. Finally, inhibition of AL512306.3 and ZEB1-AS1 significantly suppressed the cell proliferation in colon cancer cells. These results provide novel insights into the pathogenesis of colon cancer and offer promising biomarkers with the potential to guide research on carcinogenesis and cancer treatment.
铜死亡是一种新型细胞死亡方式，可能在预防各类癌症中发挥关键作用。目前关于铜死亡的研究有限，且参与结肠癌调控的铜死亡相关长链非编码核糖核酸（lncRNA）尚不清楚。本研究旨在识别铜死亡相关lncRNA的预后特征，并探究其在结肠癌中的潜在分子功能。临床相关性数据取自癌症基因组图谱（TCGA）数据库。使用“limma”软件包分析差异表达的铜死亡相关长链非编码核糖核酸（lncRNA）。随后，通过单变量Cox分析和共表达分析确定预后性铜死亡相关lncRNA特征（CupRLSig），并使用最小绝对收缩选择算子（LASSO）算法和Cox回归分析基于CupRLSig构建预后模型。采用Kaplan-Meier生存曲线和受试者工作特征（ROC）曲线评估该模型的预后预测能力。此外，还分析了CupRLSig的免疫图谱和药物敏感性。最后，通过体外实验验证了AL512306.3和ZEB1-AS1的功能。根据风险评分将患者分为高风险组或低风险组。与传统临床病理特征相比，基于特征的风险评分对患者生存的预测能力更强。此外，两组之间的免疫反应，如促炎反应和T细胞共抑制，存在显著差异。而且，化疗药物或抑制剂，如阿昔替尼、顺铂、多柔比星和依斯氯醇，可被视为高风险组患者的潜在治疗药物。最后，抑制AL512306.3和ZEB1-AS1可显著抑制结肠癌细胞的增殖。这些结果为结肠癌的发病机制提供了新见解，并提供了有前景的生物标志物，有望指导癌症发生和癌症治疗的研究。
