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单细胞测序揭示新型增殖细胞类型:在肾癌预后和治疗反应中的关键角色。

Single-cell sequencing reveals novel proliferative cell type: a key player in renal cell carcinoma prognosis and therapeutic response.

机构信息

School of Clinical Medicine, Yangzhou Polytechnic College, Yangzhou, China.

Department of Urology, Changhai Hospital, Naval Medical University (Second Military Medical University), Shanghai, China.

出版信息

Clin Exp Med. 2024 Jul 25;24(1):167. doi: 10.1007/s10238-024-01424-x.

Abstract

Renal cell carcinoma (RCC) is characterized by a variety of subtypes, each defined by unique genetic and morphological features. This study utilizes single-cell RNA sequencing to explore the molecular heterogeneity of RCC. A highly proliferative cell subset, termed as "Prol," was discovered within RCC tumors, and its increased presence was linked to poorer patient outcomes. An artificial intelligence network, encompassing traditional regression, machine learning, and deep learning algorithms, was employed to develop a Prol signature capable of predicting prognosis. The signature demonstrated superior performance in predicting RCC prognosis compared to other signatures and exhibited pan-cancer prognostic capabilities. RCC patients with high Prol signature scores exhibited resistance to targeted therapies and immunotherapies. Furthermore, the key gene CEP55 from the Prol signature was validated by both proteinomics and quantitative real time polymerase chain reaction. Our findings may provide new insights into the molecular and cellular mechanisms of RCC and facilitate the development of novel biomarkers and therapeutic targets.

摘要

肾细胞癌(RCC)具有多种亚型,每种亚型都具有独特的遗传和形态特征。本研究利用单细胞 RNA 测序来探究 RCC 的分子异质性。在 RCC 肿瘤中发现了一个具有高增殖能力的细胞亚群,称为“Prol”,其存在增加与患者预后较差相关。一个包含传统回归、机器学习和深度学习算法的人工智能网络被用于开发能够预测预后的 Prol 特征。该特征在预测 RCC 预后方面的表现优于其他特征,并且具有泛癌症预后能力。具有高 Prol 特征评分的 RCC 患者对靶向治疗和免疫治疗有抵抗性。此外,Prol 特征中的关键基因 CEP55 已通过蛋白质组学和定量实时聚合酶链反应得到验证。我们的发现可能为 RCC 的分子和细胞机制提供新的见解,并有助于开发新的生物标志物和治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4ef/11272756/6e044ebe5d0d/10238_2024_1424_Fig1_HTML.jpg

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