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Supplementary Table 2_Predictive power of genes and signatures_Patient cohorts GEO accession number from A Rare Subset of Primary Tumor Cells with Concomitant Hyperactivation of Extracellular Matrix Remodeling and dsRNA-IFN1 Signaling Metastasizes in Breast Cancer

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posted on 2023-07-05, 08:40 authored by Niccolò Roda, Andrea Cossa, Roman Hillje, Andrea Tirelli, Federica Ruscitto, Stefano Cheloni, Chiara Priami, Alberto Dalmasso, Valentina Gambino, Giada Blandano, Andrea Polazzi, Paolo Falvo, Elena Gatti, Luca Mazzarella, Lucilla Luzi, Enrica Migliaccio, Pier Giuseppe Pelicci

Supplementary Table including information about the predictive power of genes and signatures identified from metastatic clones and patient cohorts GEO accession numbers

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Italian Ministry of University and Research

Fondazione IEO-CCM

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ARTICLE ABSTRACT

Metastatic breast cancer has a poor prognosis and is largely considered incurable. A better understanding of the molecular determinants of breast cancer metastasis could facilitate development of improved prevention and treatment strategies. We used lentiviral barcoding coupled to single-cell RNA sequencing to trace clonal and transcriptional evolution during breast cancer metastasis and showed that metastases derive from rare prometastatic clones that are underrepresented in primary tumors. Both low clonal fitness and high metastatic potential were independent of clonal origin. Differential expression and classification analyses revealed that the prometastatic phenotype was acquired by rare cells characterized by the concomitant hyperactivation of extracellular matrix remodeling and dsRNA-IFN signaling pathways. Notably, genetic silencing of key genes in these pathways (KCNQ1OT1 or IFI6, respectively) significantly impaired migration in vitro and metastasis in vivo, with marginal effects on cell proliferation and tumor growth. Gene expression signatures derived from the identified prometastatic genes predict metastatic progression in patients with breast cancer, independently of known prognostic factors. This study elucidates previously unknown mechanisms of breast cancer metastasis and provides prognostic predictors and therapeutic targets for metastasis prevention. Transcriptional lineage tracing coupled with single-cell transcriptomics defined the transcriptional programs underlying metastatic progression in breast cancer, identifying prognostic signatures and prevention strategies.

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