Zhao Hongtao, Wu Lei, Liao Qinyuan, Huang Peiluo, Sun Ruonan, Yang Xiuzhen, Du Juan
Department of Immunology, College of Basic Medicine, Guilin Medical University, Guilin 541199, Guangxi, China.
College of continuing education, Guilin Medical University, Guilin 541004, China.
J Cancer. 2023 May 21;14(9):1499-1514. doi: 10.7150/jca.82370. eCollection 2023.
Lung squamous cell carcinoma has so far lacked effective targets for diagnosis and treatment. In cancer research, long noncoding RNAs (LncRNAs) emerge as novel therapeutic targets and biomarkers. Cuprophosis is a new death type involving multiple biological processes in tumor cells. Here, we aimed to explore whether Cuprophosis-related lncRNAs could be used to predict prognosis, assess immune function, and test drug sensitivity in LUSC patients. The Cancer Genome Map (TCGA) was used to obtain genome and clinical data, and Cuprophosis-relevant genes were found in the literature. A cuproptosis-related lncRNA risk model was built using co-expression analysis, univariate/multivariate Cox regression, and LASSO analysis. The survival analysis was used to assess the model's prognostic value. The univariate and multivariate Cox regression analyses were performed to determine whether risk score, age, gender, or clinical stages could be used as independent prognostic factors. Gene Set Enrichment Analysis and mutation analysis were performed on differentially expressed mRNA between high-risk and low-risk groups. The (TIDE) algorithm was used to conduct immunological functional analysis and drug sensitivity testing. Five cuproptosis-related LncRNAs were identified, and the selected LncRNAs constructed a prognosis model. According to the Kaplan-Meier survival analysis, the overall survival time for patients in the high-risk group was shorter than for those in the low-risk group. For LUSC patients, the risk score serves as an independent prognostic indicator. The GO and KEGG enrichment analysis revealed that the differentially expressed mRNAs between the high- and low-risk groups were enriched in several immune-related processes. The enrichment score of differentially expressed mRNAs in the high-risk group is higher than that of the low-risk group in multiple immune function pathways, including the IFN-γ and MHC I pathways. The Tumor Immune Dysfunction and Exclusion (TIDE) test revealed that the high-risk group was more likely to experience immune escape. The drug sensitivity analysis showed that patients with low-risk ratings were likely to respond to GW441756 and Salubrinal. In contrast, patients with higher risk scores were more responsive to dasatinib and Z-LLNIe CHO. The 5-Cuprophosis-related lncRNA signature can be used to predict prognosis, assess immune function, and test drug sensitivity in LUSC patients.
迄今为止，肺鳞状细胞癌一直缺乏有效的诊断和治疗靶点。在癌症研究中，长链非编码RNA（lncRNAs）成为新的治疗靶点和生物标志物。铜死亡是一种涉及肿瘤细胞多个生物学过程的新的死亡类型。在此，我们旨在探讨与铜死亡相关的lncRNAs是否可用于预测肺鳞癌（LUSC）患者的预后、评估免疫功能及检测药物敏感性。利用癌症基因组图谱（TCGA）获取基因组和临床数据，并从文献中查找与铜死亡相关的基因。通过共表达分析、单因素/多因素Cox回归及LASSO分析构建了一个与铜死亡相关的lncRNA风险模型。采用生存分析评估该模型的预后价值。进行单因素和多因素Cox回归分析以确定风险评分、年龄、性别或临床分期是否可作为独立的预后因素。对高风险组和低风险组之间差异表达的mRNA进行基因集富集分析和突变分析。使用肿瘤免疫功能障碍与排除（TIDE）算法进行免疫功能分析和药物敏感性测试。鉴定出5种与铜死亡相关的lncRNAs，所选的lncRNAs构建了一个预后模型。根据Kaplan-Meier生存分析，高风险组患者的总生存时间短于低风险组患者。对于LUSC患者，风险评分可作为独立的预后指标。GO和KEGG富集分析显示，高风险组和低风险组之间差异表达的mRNA在多个免疫相关过程中富集。在包括IFN-γ和MHC I途径在内的多个免疫功能途径中，高风险组差异表达mRNA的富集分数高于低风险组。肿瘤免疫功能障碍与排除（TIDE）测试显示，高风险组更易发生免疫逃逸。药物敏感性分析表明，低风险评分的患者可能对GW441756和Salubrinal有反应。相反，风险评分较高的患者对达沙替尼和Z-LLNIe CHO更敏感。5种与铜死亡相关的lncRNA特征可用于预测LUSC患者的预后、评估免疫功能及检测药物敏感性。
