Shi Yinli, Sheng Pei, Guo Ming, Chen Kai, Zhou Hongguang, Wu Mianhua, Li Wenting, Li Bo
The First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, China.
Zhongda Hospital Southeast University, Southeast University, Nanjing, China.
Front Genet. 2023 Jul 4;14:1100909. doi: 10.3389/fgene.2023.1100909. eCollection 2023.
To estimate the survival and prognosis of patients with thyroid carcinoma (THCA) based on the Long non-coding RNA (lncRNA) traits linked to cuproptosis and to investigate the connection between the immunological spectrum of THCA and medication sensitivity. RNA-Seq data and clinical information for THCA were obtained from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. We built a risk prognosis model by identifying and excluding lncRNAs associated with cuproptosis using Cox regression and LASSO methods. Both possible biological and immune infiltration functions were investigated using Principal Component Analysis (PCA), Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and immunoassays. The sensitivity of the immune response to possible THCA medicines was assessed using ratings for tumor immune dysfunction and exclusion (TIDE) and tumor mutational burden (TMB). Seven cuproptosis-related lncRNAs were used to construct our prognostic prediction model: AC108704.1, DIO3OS, AL157388.1, AL138767.3, STARD13-AS, AC008532.1, and PLBD1-AS1. Using data from TCGA's training, testing, and all groups, Kaplan-Meier and ROC curves demonstrated this feature's adequate predictive validity. Different clinical characteristics have varying effects on cuproptosis-related lncRNA risk models. Further analysis of immune cell infiltration and single sample Gene Set Enrichment Analysis (ssGSEA) supported the possibility that cuproptosis-associated lncRNAs and THCA tumor immunity were closely connected. Significantly, individuals with THCA showed a considerable decline in survival owing to the superposition effect of patients in the high-risk category and high TMB. Additionally, the low-risk group had a higher TIDE score compared with the high-risk group, indicating that these patients had suboptimal immune checkpoint blocking responses. To ensure the accuracy and reliability of our results, we further verified them using several GEO databases. The clinical and risk aspects of cuproptosis-related lncRNAs may aid in determining the prognosis of patients with THCA and improving therapeutic choices.
基于与铜死亡相关的长链非编码RNA(lncRNA)特征评估甲状腺癌(THCA)患者的生存和预后,并研究THCA的免疫谱与药物敏感性之间的联系。从癌症基因组图谱(TCGA)和基因表达综合数据库(GEO)获取THCA的RNA测序数据和临床信息。我们使用Cox回归和LASSO方法识别并排除与铜死亡相关的lncRNA,构建了一个风险预后模型。使用主成分分析(PCA)、基因本体论(GO)、京都基因与基因组百科全书(KEGG)和免疫分析研究了可能的生物学和免疫浸润功能。使用肿瘤免疫功能障碍和排除评分(TIDE)以及肿瘤突变负荷(TMB)评估免疫反应对可能的THCA药物的敏感性。使用7个与铜死亡相关的lncRNA构建我们的预后预测模型:AC108704.1、DIO3OS、AL157388.1、AL138767.3、STARD13-AS、AC008532.1和PLBD1-AS1。使用来自TCGA的训练组、测试组和所有组的数据,Kaplan-Meier曲线和ROC曲线证明了该特征具有足够的预测效度。不同的临床特征对与铜死亡相关的lncRNA风险模型有不同影响。对免疫细胞浸润和单样本基因集富集分析(ssGSEA)的进一步分析支持了与铜死亡相关的lncRNA和THCA肿瘤免疫密切相关的可能性。值得注意的是,由于高危类别患者和高TMB的叠加效应,THCA患者的生存率显著下降。此外,低风险组的TIDE评分高于高风险组,表明这些患者的免疫检查点阻断反应欠佳。为确保结果的准确性和可靠性,我们使用多个GEO数据库进行了进一步验证。与铜死亡相关的lncRNA的临床和风险方面可能有助于确定THCA患者的预后并改善治疗选择。