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通过单细胞RNA测序见解探索肿瘤相关基因在透明细胞肾细胞癌中的预后价值

Exploring the Prognostic Value of Tumour-Associated Genes in Clear Cell Renal Cell Carcinoma Through Single-Cell RNA Sequencing Insights.

作者信息

Fu Tongfei, Zhang Xinyi, Liu Yuedong, Wu Junsong, Liu Xuefeng, Lu Bichao, Huang Yi, Yang Liping, Zhan Yongli

机构信息

Department of Nephrology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China.

The First Clinical College, Hubei University of Chinese Medicine, Wuhan, China.

出版信息

J Cell Mol Med. 2024 Dec;28(24):e70297. doi: 10.1111/jcmm.70297.

DOI:10.1111/jcmm.70297
PMID:39706820
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11661917/
Abstract

Clear cell renal cell carcinoma (ccRCC) characterised by its diversity and a tendency to defy standard therapeutic approaches. Amidst the advent of immunotherapy, it has become imperative to pinpoint prognostic indicators of the tumour microenvironment (TME) influence the efficacy of treatments. Employing single-cell RNA sequencing (scRNA-seq), this research delved into the diverse landscape of ccRCC, uncovering its complex underpinnings and pinpointing molecular avenues for therapeutic intervention. We constructed a prognostic model using 101 machine learning algorithms and integrated data from multiple cohorts, including TCGA, ICGC, and microarray datasets. The model's efficacy was assessed using the Concordance Index (C-index), and further analyses included pseudotime analysis of tumour cells, mutation analysis and correlation analysis between the prognostic model and tumour immunity. The prognostic model, combining Lasso regression and survival Support Vector Machine (SVM), demonstrated robust discrimination with a C-index of 0.650. Investigation into the TME uncovered pronounced associations between the presence of immune cell infiltrates and patient outcomes, with a notable emphasis on the impact of CCL2-expressing neoplastic cells. The GO Biological Processes (GOBP) encompass the regulation of endothelial cell maturation, the formation of endothelial layers, the enhancement of gene expression controlled by Notch receptors, and the development of endothelial barriers. The research effectively pinpointed critical prognostic markers and crafted a forecasting model that achieved a C-index of 0.650, highlighting the significant impact of immune cell infiltration, especially CCL2+ neoplastic cells, on ccRCC patient prognosis.

摘要

透明细胞肾细胞癌(ccRCC)具有多样性且往往对标准治疗方法产生抵抗。在免疫疗法出现的背景下,确定肿瘤微环境(TME)影响治疗效果的预后指标变得至关重要。本研究采用单细胞RNA测序(scRNA-seq)深入探究ccRCC的多样图景,揭示其复杂的内在机制并确定治疗干预的分子途径。我们使用101种机器学习算法构建了一个预后模型,并整合了来自多个队列的数据,包括TCGA、ICGC和微阵列数据集。使用一致性指数(C-index)评估模型的有效性,进一步的分析包括肿瘤细胞的伪时间分析、突变分析以及预后模型与肿瘤免疫之间的相关性分析。结合套索回归和生存支持向量机(SVM)的预后模型显示出强大的区分能力,C-index为0.650。对TME的研究发现免疫细胞浸润的存在与患者预后之间存在显著关联,尤其强调表达CCL2的肿瘤细胞的影响。基因本体生物学过程(GOBP)包括内皮细胞成熟的调节、内皮层的形成、Notch受体控制的基因表达增强以及内皮屏障的发育。该研究有效地确定了关键的预后标志物并构建了一个C-index为0.650的预测模型,突出了免疫细胞浸润,尤其是CCL2 +肿瘤细胞对ccRCC患者预后的重大影响。

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