Emergence of high-metastatic potentials and prediction of recurrence and metastasis

Article Article scientifique Article Emergence of high-metastatic potentials and prediction of recurrence and metastasis eng 2025-12-23 2026-01-27 author Srinivasan Aravind Department of Medical Genetics and Development, University of Geneva Medical School, Geneva, Switzerland. 988312 Département de médecine génétique et développement (GEDEV) author Conod Arwen Department of Medical Genetics and Development, University of Geneva Medical School, Geneva, Switzerland. 583815 Département de médecine génétique et développement (GEDEV) author Tapponnier Yann Department of Medical Genetics and Development, University of Geneva Medical School, Geneva, Switzerland. 892698 author Silvano Marianna Department of Medical Genetics and Development, University of Geneva Medical School, Geneva, Switzerland. 859998 Département de médecine génétique et développement (GEDEV) author Dall'Olio Luca Department of Medical Genetics and Development, University of Geneva Medical School, Geneva, Switzerland. 966968 author Delucinge Céline IGE3 Genomics Platform, University of Geneva, Geneva, Switzerland. 135758 plan stratégique sciences vie médecine (PSVIM) author Borges Grazina Ana Isabel Department of Medical Genetics and Development, University of Geneva Medical School, Geneva, Switzerland. 135554 Département de médecine génétique et développement (GEDEV) author Ruiz Altaba Ariel Department of Medical Genetics and Development, University of Geneva Medical School, Geneva, Switzerland; IGE3 Institue, University of Geneva, Geneva, Switzerland. Electronic address: ariel.ruizaltaba@unige.ch. 135639 Département de médecine génétique et développement (GEDEV) 116834 10.1016/j.celrep.2025.116834 41447536 2211-1247 https://www.sciencedirect.com/science/article/pii/S2211124725016067 What makes a cancer highly metastatic is not known. Here, we inquire on the metastatic potential (MP) of tumor cells, which reflects their probability to emigrate from the primary tumor to new sites to form secondary cancers. We determine the transcriptomic landscapes of single-cell-derived clones in hybrid EMT space and define metastatic potential gradient genes (MPGGs) that linearly track MP strength. Perturbation of selected MPGGs and linked processes reveals a dynamic cellular and molecular framework of what we define as "cell-state ensembles" underlying the emergence of high MPs. To test if MPGGs predict cancer recurrence, we build the MangroveGS machine-learning model with "gene signature ensembles": MangroveGS<sup>MPGGs</sup> robustly predicts patient tumor recurrence and metastases, outperforms all other signatures and staging systems tested, and can be extended to multiple cancer types of epithelial nature. Our findings uncover an unsuspected shared strategy for the onset of metastases that underlies clinical outcome. CP: cancer Cancer Cell states Disease recurrence Ensemble Gradient Metastasis Metastatic potential Plasticity Prediction Risk Dewey 590 Dewey 576.5 Swiss Cancer Research Foundation KFS-4965-02-2020 135 Département de médecine génétique et développement 21D 23 Institut de génétique et de génomique 0DH false 446 Stemness dans le développement et les maladies: Signalisation, reprogrammation et mécanismes des métastases 776 https://zenodo.org/records/17787369 Cell reports 45 1 04333a78-fe25-45bf-aec5-6914c149150d Article (Published version) Public Emergence_of_high-metastatic.pdf 22506952 application/pdf CC BY-NC-ND-4.0 1fbfac8581b9f78c1e468b8c9a6ff904f2bfc5b948fc96dd947bf854b870a7e8 516c560a-9667-4d6c-b8d2-9e5707805743 Supplemental data Public 1-s2.0-S2211124725016067-mmc1.pdf 13397825 application/pdf 6258da6869ec3e640335081d5be5baf7be4fa7bf020ab699a867ab9972b7235d 1b75929f-51cd-4486-9188-7875b9641aa8 Supplemental data Public 1-s2.0-S2211124725016067-mmc2.xlsx 64138 application/vnd.openxmlformats-officedocument.spreadsheetml.sheet 005683275ae440ab52f88441c1ff638e5acee0b55e55987f9935277fb914be41 65c9eca1-fa72-4ca4-a3f7-dc118ddc6a42 Supplemental data Public 1-s2.0-S2211124725016067-mmc3.xls 82944 application/vnd.ms-excel fde8de7d20b03de190c9207538c164af8b63208fb812eef3cb9003e4a2556326 3f9d6254-be11-425b-b19f-1ea0baf714ae Supplemental data Public 1-s2.0-S2211124725016067-mmc4.pdf 36130803 application/pdf 35bfd6997c21df180119cc14711a271b4f1e0101b9fa6aa150f5edd389da6fb2 Vignette Public 1-s2.0-S2211124725016067-fx1_lrg.jpg 290502 image/png openAccess Faculté de médecine / Section de médecine fondamentale / Département de médecine génétique et développement Centres et instituts / Institut de génétique et de génomique

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Emergence of high-metastatic potentials and prediction of recurrence and metastasis	Cell reports			2026	2	1

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Srinivasan, Aravind