Department of Urology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China.
Peking University Fifth School of Clinical Medicine, Beijing, China.
Medicine (Baltimore). 2023 Oct 13;102(41):e35196. doi: 10.1097/MD.0000000000035196.
Bladder cancer (BC) is a leading cause of male cancer-related deaths globally. Immunotherapy is showing promise as a treatment option for BC. Numerous studies suggested that necroptosis and long noncoding RNAs (lncRNAs) were critical players in the development of cancers and interacting with cancer immunity. However, the prognostic value of necroptosis-related lncRNAs and their impact on immunotherapeutic response in patients with BC have yet to be well examined. Thus, this study aims to find new biomarkers for predicting prognosis and determining immune subtypes of BC to select appropriate patients from a heterogeneous population. The clinicopathology and transcriptome information from The Cancer Genome Atlas (TCGA) was downloaded, and coexpression analysis was performed to identify necroptosis-related lncRNAs. Then LASSO regression was employed to construct a prediction signature. The signature performance was evaluated by Kaplan-Meier (K-M) method, Time-dependent receiver operating characteristics (ROC). The functional enrichment, immune infiltration, immune checkpoint activation, and the half-maximal inhibitory concentration (IC50) of common drugs in risk groups were compared. The consensus clustering analysis based on lncRNAs associated with necroptosis was made to get 2 clusters to identify hot and cold tumors further. Lastly, the immune response between cold and hot tumors was discussed. In this study, a model containing 5 necroptosis-related lncRNAs was constructed. The risk score distribution of these lncRNAs was compared between low- and high-risk groups in the training, testing, and entire sets. K-M analysis showed that the low-risk patients had significantly better prognosis. The area under the ROC curve (AUC) for the 1-, 3-, and 5-year ROC curves in the entire sets were 0.690, 0.709, and 0.722, respectively. High-risk patients were enriched in lncRNAs related to tumor immunity and had better immune cell infiltration and immune checkpoint activation. Hot tumors and cold tumors were effectively distinguished by clusters 1 and cluster 2, respectively. We developed a necroptosis-related signature based on 5 prognostic lncRNAs, expected to become a new tool for evaluating the prognosis of patients with BC and classifying hot or cold tumors, thus facilitating the development of precision therapy for BC.
膀胱癌（BC）是全球男性癌症相关死亡的主要原因。免疫疗法作为 BC 的一种治疗选择显示出前景。许多研究表明，细胞坏死和长链非编码 RNA（lncRNA）是癌症发展的关键因素，与癌症免疫相互作用。然而，细胞坏死相关 lncRNA 的预后价值及其对 BC 患者免疫治疗反应的影响尚未得到很好的研究。因此，本研究旨在寻找新的生物标志物来预测预后，并确定 BC 的免疫亚型，以便从异质人群中选择合适的患者。从癌症基因组图谱（TCGA）下载临床病理和转录组信息，并进行共表达分析以鉴定细胞坏死相关 lncRNA。然后使用 LASSO 回归构建预测特征。通过 Kaplan-Meier（K-M）方法、时间依赖性接收器操作特征（ROC）评估特征的性能。比较风险组的功能富集、免疫浸润、免疫检查点激活和常见药物的半最大抑制浓度（IC50）。基于与细胞坏死相关的 lncRNA 进行共识聚类分析，得到 2 个聚类，进一步识别热肿瘤和冷肿瘤。最后，讨论了冷肿瘤和热肿瘤之间的免疫反应。在这项研究中，构建了一个包含 5 个细胞坏死相关 lncRNA 的模型。在训练、测试和整个数据集的低风险和高风险组之间比较这些 lncRNA 的风险评分分布。K-M 分析表明，低风险患者的预后明显更好。整个数据集的 1 年、3 年和 5 年 ROC 曲线的 AUC 分别为 0.690、0.709 和 0.722。高风险患者富集了与肿瘤免疫相关的 lncRNA，具有更好的免疫细胞浸润和免疫检查点激活。通过聚类 1 和聚类 2，有效地区分了热肿瘤和冷肿瘤。我们基于 5 个预后 lncRNA 开发了一个细胞坏死相关的特征，有望成为评估 BC 患者预后和分类热肿瘤或冷肿瘤的新工具，从而促进 BC 精准治疗的发展。
