One-carbon metabolic pathway is a novel molecular signature for CD44-positive intestinal-type gastric cancer.

IF 7 2区生物学 Q1 CELL BIOLOGY

Cell Death Discovery Pub Date : 2025-08-23 DOI:10.1038/s41420-025-02704-5

Seyeon Joo, Yoojin Bae, Bo Kyung Yoon, Yeonjin Je, Yuna Kim, Minki Kim, Su-Jin Shin, Sungsoon Fang, Jie-Hyun Kim

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引用次数: 0

Abstract

Intratumoral heterogeneity (ITH), arising from various factors, plays a crucial role in diverse cancers, yet research on ITH remains in its early stages. To explore this phenomenon further, we conducted single-nuclei transcriptome profiling on patient-derived organoids (PDOs) from two histologically pure subtypes of gastric cancer. We identified differences in cancer stem cell marker expression among intestinal-type samples and their correlation with one-carbon (1C) metabolism. Notably, some gastric cancer samples, although histologically classified as intestinal-type, exhibited diffuse-like genetic characteristics. This finding suggests the potential for employing a 1C metabolism inhibition strategy as a therapeutic approach for these genetically diffuse-like gastric cancers. This study highlights the necessity of addressing ITH in PDO-based preclinical models and contributes valuable insights toward advancing precision medicine treatments for gastric cancer.

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单碳代谢途径是cd44阳性肠型胃癌的一个新的分子特征。

由多种因素引起的肿瘤内异质性（intratumumheterogeneity， ITH）在多种癌症中起着至关重要的作用，但对ITH的研究仍处于早期阶段。为了进一步探索这一现象，我们对来自两种组织学纯粹的胃癌亚型的患者源性类器官（PDOs）进行了单核转录组分析。我们确定了肠型样本中癌症干细胞标志物表达的差异及其与一碳（1C）代谢的相关性。值得注意的是，一些胃癌样本虽然在组织学上被归类为肠型，但却表现出弥漫性样遗传特征。这一发现提示采用1C代谢抑制策略作为这些基因弥漫性胃癌的治疗方法的潜力。本研究强调了在基于pdo的临床前模型中解决ITH的必要性，并为推进胃癌的精准医学治疗提供了有价值的见解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cell Death Discovery Biochemistry, Genetics and Molecular Biology-Cell Biology

CiteScore

8.30

自引率

1.40%

发文量

468

审稿时长

9 weeks

期刊介绍： Cell Death Discovery is a multidisciplinary, international, online-only, open access journal, dedicated to publishing research at the intersection of medicine with biochemistry, pharmacology, immunology, cell biology and cell death, provided it is scientifically sound. The unrestricted access to research findings in Cell Death Discovery will foster a dynamic and highly productive dialogue between basic scientists and clinicians, as well as researchers in industry with a focus on cancer, neurobiology and inflammation research. As an official journal of the Cell Death Differentiation Association (ADMC), Cell Death Discovery will build upon the success of Cell Death & Differentiation and Cell Death & Disease in publishing important peer-reviewed original research, timely reviews and editorial commentary. Cell Death Discovery is committed to increasing the reproducibility of research. To this end, in conjunction with its sister journals Cell Death & Differentiation and Cell Death & Disease, Cell Death Discovery provides a unique forum for scientists as well as clinicians and members of the pharmaceutical and biotechnical industry. It is committed to the rapid publication of high quality original papers that relate to these subjects, together with topical, usually solicited, reviews, editorial correspondence and occasional commentaries on controversial and scientifically informative issues.