Department and Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, 430030 Wuhan, China.
Department of Gynecology and Obstetrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, 430030 Wuhan, China.
Dis Markers. 2022 Mar 23;2022:8131007. doi: 10.1155/2022/8131007. eCollection 2022.
Epithelial-mesenchymal transition (EMT) plays a vital role in tumor metastasis and drug resistance. It has been reported that EMT is regulated by several long noncoding RNAs (lncRNAs). We aimed to identify EMT-related lncRNAs and develop an EMT-related lncRNA prognostic signature in kidney renal clear cell carcinoma (KIRC).
In total, 530 ccRCC patients with 611 transcriptome profiles were included in this study. We first identified differentially expressed EMT-related lncRNAs. Then, all the samples with transcriptional data and clinical survival information were randomly split into training/test sets at a ratio of 1 : 1. Accordingly, we further developed a twelve differentially expressed EMT-related lncRNA prognostic signature in the training set. Following this, risk analysis, survival analysis, subgroup analysis, and the construction of the ROC curves were applied to verify the efficacy of the signature in the training set, test set, and all patients. Besides, we further investigated the differential immune infiltration, immune checkpoint expression, and immune-related functions between high-risk patients. Finally, we explored the different drug responses to targeted therapy (sunitinib and sorafenib) and immunotherapy (anti-PD1 and anti-CTLA4).
A twelve differentially expressed EMT-related lncRNA prognostic signature performed superior in predicting the overall survival of KIRC patients. High-risk patients were observed with a significantly higher immune checkpoint expression and showed better responses to the targeted therapy and immunotherapy.
Our study demonstrates that the twelve differentially expressed EMT-related lncRNA prognostic signature could act as an efficient prognostic indicator for KIRC, which also contributes to the decision-making of the further treatment.
上皮-间充质转化（EMT）在肿瘤转移和耐药中起着至关重要的作用。已有报道称 EMT 受几种长链非编码 RNA（lncRNA）的调控。我们旨在鉴定 EMT 相关的 lncRNA，并开发肾透明细胞癌（KIRC）中 EMT 相关 lncRNA 的预后标志。
本研究共纳入了 530 例有 611 个转录组谱的 ccRCC 患者。我们首先鉴定了差异表达的 EMT 相关 lncRNA。然后，所有具有转录数据和临床生存信息的样本被随机分为训练/测试集，比例为 1:1。据此，我们进一步在训练集中开发了一个由 12 个差异表达 EMT 相关 lncRNA 组成的预后签名。随后，风险分析、生存分析、亚组分析和 ROC 曲线的构建用于验证该签名在训练集、测试集和所有患者中的疗效。此外，我们进一步研究了高危患者之间的差异免疫浸润、免疫检查点表达和免疫相关功能。最后，我们探索了针对靶向治疗（舒尼替尼和索拉非尼）和免疫治疗（抗 PD1 和抗 CTLA4）的不同药物反应。
一个由 12 个差异表达 EMT 相关 lncRNA 组成的预后签名在预测 KIRC 患者的总生存率方面表现出色。高危患者的免疫检查点表达明显更高，并对靶向治疗和免疫治疗有更好的反应。
我们的研究表明，12 个差异表达 EMT 相关 lncRNA 的预后签名可以作为 KIRC 的有效预后指标，有助于进一步治疗决策。
