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一个与 Notch 信号相关的 lncRNA 特征,可预测肾透明细胞癌的预后和治疗反应。

A Notch signaling-related lncRNA signature for predicting prognosis and therapeutic response in clear cell renal cell carcinoma.

机构信息

Department of Medical Research Center, Shaoxing People's Hospital, No.568, Zhongxing North Road, Shaoxing, 312000, Zhejiang Province, China.

Department of Urology, Shaoxing People's Hospital, No.568, Zhongxing North Road, Shaoxing, 312000, Zhejiang Province, China.

出版信息

Sci Rep. 2023 Nov 30;13(1):21141. doi: 10.1038/s41598-023-48596-2.

DOI:10.1038/s41598-023-48596-2
PMID:38036719
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10689792/
Abstract

Increasing evidence has confirmed the vital role of Notch signaling in the tumorigenesis of clear cell renal cell carcinoma (ccRCC). The underlying function of long non-coding RNA (lncRNA) related to Notch signaling in ccRCC remains unclear. In present study, the prognostic value and therapeutic strategy of Notch signaling-related lncRNA are comprehensively explored in ccRCC. In total, we acquired 1422 NSRlncRNAs, of which 41 lncRNAs were identified the key NSRlncRNAs associated with the occurrence of ccRCC. The prognostic signature containing five NSRlncRNAs (AC092611.2, NNT-AS1, AGAP2-AS1, AC147651.3, and AC007406.3) was established and validated, and the ccRCC patients were clustered into the high- and low-risk groups. The overall survival of patients in the low-risk group were much more favorable than those in the high-risk group. Multivariate Cox regression analysis indicated that the risk score was an independent prognostic biomarker. Based on the risk score and clinical variables, a nomogram for predicting prognosis of ccRCC patients was constructed, and the calibration curves and DCA curves showed the superior predictive ability of nomogram. The risk score was correlated with immune cell infiltration, targeted therapy or chemotherapy sensitivity, and multiple oncogenic pathways. Additionally, consensus clustering analysis stratified the ccRCC patients into four clusters with obvious different outcomes, immune microenvironments, and expression of immune checkpoints. The constructed NSRlncRNA-based signature might serve as a potential biomarker for predicting prognosis and response to immunotherapy or targeted therapy in patients with ccRCC.

摘要

越来越多的证据证实了 Notch 信号在透明细胞肾细胞癌 (ccRCC) 发生中的重要作用。Notch 信号相关长链非编码 RNA (lncRNA)在 ccRCC 中的潜在功能尚不清楚。在本研究中,全面探讨了 Notch 信号相关 lncRNA 在 ccRCC 中的预后价值和治疗策略。我们共获得了 1422 个 NSRlncRNAs,其中 41 个 lncRNA 被确定为与 ccRCC 发生相关的关键 NSRlncRNA。包含五个 NSRlncRNAs(AC092611.2、NNT-AS1、AGAP2-AS1、AC147651.3 和 AC007406.3)的预后特征被建立和验证,ccRCC 患者被聚类为高低风险组。低风险组患者的总生存率明显优于高风险组。多因素 Cox 回归分析表明,风险评分是一个独立的预后生物标志物。基于风险评分和临床变量,构建了一个预测 ccRCC 患者预后的列线图,校准曲线和 DCA 曲线显示了列线图的优越预测能力。风险评分与免疫细胞浸润、靶向治疗或化疗敏感性以及多个致癌通路相关。此外,共识聚类分析将 ccRCC 患者分为四个具有明显不同结局、免疫微环境和免疫检查点表达的聚类。构建的基于 NSRlncRNA 的特征可能成为预测 ccRCC 患者预后和对免疫治疗或靶向治疗反应的潜在生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b7e1/10689792/0aac10e04b47/41598_2023_48596_Fig12_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b7e1/10689792/45405f6fdaca/41598_2023_48596_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b7e1/10689792/19f3ccc3969b/41598_2023_48596_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b7e1/10689792/f7214dd68186/41598_2023_48596_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b7e1/10689792/ce1c0a8c6932/41598_2023_48596_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b7e1/10689792/8f1de39106ef/41598_2023_48596_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b7e1/10689792/f713f3b418f6/41598_2023_48596_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b7e1/10689792/d186f87b1509/41598_2023_48596_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b7e1/10689792/8b58f9a16e19/41598_2023_48596_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b7e1/10689792/3605348a9d09/41598_2023_48596_Fig10_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b7e1/10689792/edc4018a2c41/41598_2023_48596_Fig11_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b7e1/10689792/0aac10e04b47/41598_2023_48596_Fig12_HTML.jpg

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