Clonal dispersal is associated with tumor heterogeneity and poor prognosis in colorectal cancer

IF 4.1 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES iScience Pub Date : 2025-04-10 DOI:10.1016/j.isci.2025.112403

Selami Baglamis , Vivek M. Sheraton , Sanne M. van Neerven , Adrian Logiantara , Lisanne E. Nijman , Laura A. Hageman , Nicolas Léveillé , Clara C. Elbers , Maarten F. Bijlsma , Louis Vermeulen , Przemek M. Krawczyk , Kristiaan J. Lenos

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Abstract

Clonal dispersal, resulting from the intermingling of tumor cell subpopulations, is thought to be a key driver of tumor heterogeneity. Despite advances in spatial modeling of cancer biology, quantification of clonal dispersal has been challenging. This study introduces a straightforward method, relying on fluorescent cell barcoding, to quantify clonal dispersal in various in vitro and in vivo models of colorectal cancer (CRC). Our approach allows for precise localization of clones and uncovering the degree of clonal mixing across different CRC models. Our findings suggest that clonal dispersal is correlated with the expression of genes involved in epithelial-mesenchymal transition and CMS4-related signaling pathways. We further identify a dispersal gene signature, associated with intratumor heterogeneity, which is a robust clinical predictor of poor prognosis and recurrence in CRC, highlighting its potential as a prognostic marker and a putative direction for therapeutic targeting.

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克隆分散与结直肠癌的肿瘤异质性和不良预后相关

克隆分散是肿瘤细胞亚群相互混合的结果，被认为是肿瘤异质性的主要驱动因素。尽管癌症生物学的空间建模取得了进展，但克隆扩散的量化一直是个难题。本研究介绍了一种依靠荧光细胞条形码的直接方法，用于量化各种体外和体内结直肠癌（CRC）模型中的克隆分散。我们的方法可以精确定位克隆，并揭示不同 CRC 模型中克隆的混合程度。我们的研究结果表明，克隆的分散与涉及上皮-间质转化和 CMS4 相关信号通路的基因表达相关。我们进一步确定了与肿瘤内异质性相关的分散基因特征，它是预测 CRC 预后不良和复发的可靠临床指标，突出了其作为预后标志物的潜力和治疗靶向的可能方向。

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来源期刊

iScience Multidisciplinary-Multidisciplinary

CiteScore

7.20

自引率

1.70%

发文量

1972

审稿时长

6 weeks

期刊介绍： Science has many big remaining questions. To address them, we will need to work collaboratively and across disciplines. The goal of iScience is to help fuel that type of interdisciplinary thinking. iScience is a new open-access journal from Cell Press that provides a platform for original research in the life, physical, and earth sciences. The primary criterion for publication in iScience is a significant contribution to a relevant field combined with robust results and underlying methodology. The advances appearing in iScience include both fundamental and applied investigations across this interdisciplinary range of topic areas. To support transparency in scientific investigation, we are happy to consider replication studies and papers that describe negative results. We know you want your work to be published quickly and to be widely visible within your community and beyond. With the strong international reputation of Cell Press behind it, publication in iScience will help your work garner the attention and recognition it merits. Like all Cell Press journals, iScience prioritizes rapid publication. Our editorial team pays special attention to high-quality author service and to efficient, clear-cut decisions based on the information available within the manuscript. iScience taps into the expertise across Cell Press journals and selected partners to inform our editorial decisions and help publish your science in a timely and seamless way.