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通过单细胞分辨率分析揭示胃癌的代谢特征及临床意义

Unraveling metabolic characteristics and clinical implications in gastric cancer through single-cell resolution analysis.

作者信息

Wang Wenyue, Li Conghui, Dai Yuting, Wu Qingfa, Yu Weiqiang

机构信息

School of Life Sciences, Tianjin University, Tianjin, China.

HIM-BGI Omics Center, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences (CAS), Hangzhou, China.

出版信息

Front Mol Biosci. 2024 May 20;11:1399679. doi: 10.3389/fmolb.2024.1399679. eCollection 2024.

Abstract

Gastric cancer is a highly prevalent malignant neoplasm. Metabolic reprogramming is intricately linked to both tumorigenesis and cancer immune evasion. The advent of single-cell RNA sequencing technology provides a novel perspective for evaluating cellular metabolism. This study aims to comprehensively investigate the metabolic pathways of various cell types in tumor and normal samples at high resolution and delve into the intricate regulatory mechanisms governing the metabolic activity of malignant cells in gastric cancer. Utilizing single-cell RNA sequencing data from gastric cancer, we constructed metabolic landscape maps for different cell types in tumor and normal samples. Employing unsupervised clustering, we categorized malignant cells in tumor samples into high and low metabolic subclusters and further explored the characteristics of these subclusters. Our research findings indicate that epithelial cells in tumor samples exhibit significantly higher activity in most KEGG metabolic pathways compared to other cell types. Unsupervised clustering, based on the scores of metabolic pathways, classified malignant cells into high and low metabolic subclusters. In the high metabolic subcluster, it demonstrated the potential to induce a stronger immune response, correlating with a relatively favorable prognosis. In the low metabolic subcluster, a subset of cells resembling cancer stem cells (CSCs) was identified, and its prognosis was less favorable. Furthermore, a set of risk genes associated with this subcluster was discovered. This study reveals the intricate regulatory mechanisms governing the metabolic activity of malignant cells in gastric cancer, offering new perspectives for improving prognosis and treatment strategies.

摘要

胃癌是一种高度流行的恶性肿瘤。代谢重编程与肿瘤发生和癌症免疫逃逸密切相关。单细胞RNA测序技术的出现为评估细胞代谢提供了新的视角。本研究旨在高分辨率全面研究肿瘤和正常样本中各种细胞类型的代谢途径,并深入探讨胃癌中恶性细胞代谢活性的复杂调控机制。利用胃癌的单细胞RNA测序数据,我们构建了肿瘤和正常样本中不同细胞类型的代谢景观图。采用无监督聚类,我们将肿瘤样本中的恶性细胞分为高代谢和低代谢亚群,并进一步探索这些亚群的特征。我们的研究结果表明,与其他细胞类型相比,肿瘤样本中的上皮细胞在大多数KEGG代谢途径中表现出显著更高的活性。基于代谢途径得分的无监督聚类将恶性细胞分为高代谢和低代谢亚群。在高代谢亚群中,它显示出诱导更强免疫反应的潜力,与相对较好的预后相关。在低代谢亚群中,鉴定出了一部分类似癌症干细胞(CSC)的细胞,其预后较差。此外,还发现了一组与该亚群相关的风险基因。本研究揭示了胃癌中恶性细胞代谢活性的复杂调控机制,为改善预后和治疗策略提供了新的视角。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed2e/11145399/074acc252693/fmolb-11-1399679-g001.jpg

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