Xie Shangxun, He Jibao, Feng Baofu, Rao Dapang, Wang Shuaibin, He Youhua
Department of Urology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province 325000, People's Republic of China.
Department of Urology, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, Jiangsu Province 210028, People's Republic of China.
Heliyon. 2023 May 1;9(5):e15897. doi: 10.1016/j.heliyon.2023.e15897. eCollection 2023 May.
Bladder urothelial carcinoma (BLCA) is the second prevalent genitourinary carcinoma globally. N7-methylguanosine (m7G) is important for tumorigenesis and progression. This study aimed to build a predictive model for m7G-related long non-coding RNAs (lncRNAs), elucidate their role in the tumor immune microenvironment (TIME), and predict immunotherapy response in BLCA.
We first used univariate Cox regression and coexpression analyses to identify m7G-related lncRNAs. Next, the prognostic model was built by utilizing LASSO regression analysis. Then, the prognostic significance of the model was examined utilizing Kaplan-Meier survival analysis, receiver operating characteristic (ROC) curves, nomogram, and univariate, multivariate Cox regression. We also analyzed Gene set enrichment analyses (GSEA), immune analysis and principal component analysis (PCA) in risk groups. To further predict immunotherapy effectiveness, we evaluated the predictive ability for immunotherapy in 2 risk groups and clusters using tumor immune dysfunction and exclusion (TIDE) score and Immunophenoscore (IPS).
Seven lncRNAs related to m7G were used to create a model. The calibration plots for the model suggested a strong fit with the prediction of overall survival (OS). The area under the curve (AUC) for first, second, and third years was respectively, 0.722, 0.711, and 0.686. In addition, the risk score had strong correlation with TIME features and genes linked to immune checkpoint blockade (ICB). TIDE scores were dramatically different between two risk groups (p < 0.05), and IPS scores were markedly different between two clusters (p < 0.05).
Our research constructed a novel m7G-related lncRNAs that could be used to predict patient outcomes and the effectiveness of immunotherapy in BLCA. Immunotherapy may be more effective for the low-risk group and cluster 2.
膀胱尿路上皮癌（BLCA）是全球第二常见的泌尿生殖系统癌症。N7-甲基鸟苷（m7G）对肿瘤发生和进展至关重要。本研究旨在构建一个与m7G相关的长链非编码RNA（lncRNA）预测模型，阐明它们在肿瘤免疫微环境（TIME）中的作用，并预测BLCA中的免疫治疗反应。
我们首先使用单变量Cox回归和共表达分析来鉴定与m7G相关的lncRNA。接下来，利用LASSO回归分析建立预后模型。然后，通过Kaplan-Meier生存分析、受试者工作特征（ROC）曲线、列线图以及单变量、多变量Cox回归来检验模型的预后意义。我们还分析了风险组中的基因集富集分析（GSEA）、免疫分析和主成分分析（PCA）。为了进一步预测免疫治疗效果，我们使用肿瘤免疫功能障碍和排除（TIDE）评分和免疫表型评分（IPS）评估了两个风险组和聚类中免疫治疗的预测能力。
七个与m7G相关的lncRNA被用于创建一个模型。该模型的校准图表明与总生存期（OS）的预测具有很强的拟合度。第一年、第二年和第三年的曲线下面积（AUC）分别为0.722、0.711和0.686。此外，风险评分与TIME特征以及与免疫检查点阻断（ICB）相关的基因有很强的相关性。两个风险组之间的TIDE评分有显著差异（p < 0.05），两个聚类之间的IPS评分有显著差异（p < 0.05）。
我们的研究构建了一种新型的与m7G相关的lncRNA，可用于预测BLCA患者的预后和免疫治疗效果。免疫治疗可能对低风险组和聚类2更有效。
