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Integrated inference of cancer gene expression from cell-free plasma chromatin.

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bioRxiv : the preprint server for biology 📖 저널 OA 100% 2023: 2/2 OA 2024: 47/47 OA 2025: 299/299 OA 2026: 247/247 OA 2023~2026 2026
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Gulati GS, Vasseur D, Nawfal R, Sotudian S, Semaan K, Eid M, Seo JH, Phillips N, Canniff JJ, Savignano H, Chhetri SB, Jin Z, Ou Y, Bani MA, Mary Lee GS, Trowbridge R, Epstein IB, Rickards G, Cordeiro PRDS, Zhang Z, Chehade REH, James B, Massard C, Italiano A, Hollebecque A, Soria JC, André F, Badoual C, Bellmunt J, Singh H, Aguirre AJ, Wolpin BM, Choueiri TK, Baca SC, Freedman ML

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Gene expression is a defining determinant of tumor identity, behavior, and therapeutic response, yet remains challenging to measure noninvasively.

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APA Gulati GS, Vasseur D, et al. (2026). Integrated inference of cancer gene expression from cell-free plasma chromatin.. bioRxiv : the preprint server for biology. https://doi.org/10.64898/2026.02.18.706026
MLA Gulati GS, et al.. "Integrated inference of cancer gene expression from cell-free plasma chromatin.." bioRxiv : the preprint server for biology, 2026.
PMID 41756975 ↗

Abstract

Gene expression is a defining determinant of tumor identity, behavior, and therapeutic response, yet remains challenging to measure noninvasively. Here, we introduce APEX (Associating Plasma Epigenomic features with eXpression), a framework for inferring expression from circulating cell-free chromatin. Trained on ~270,000 gene-sample pairs from matched tumor RNA-seq and plasma cfChIP-seq across multiple cancers and validated on >15 unseen cancer subtypes, APEX accurately infers cancer gene expression across a range of tumor fractions and outperforms existing plasma-based approaches by integrating positional histone mark and DNA fragmentation patterns across promoters and gene bodies. Using plasma alone, APEX enables classification of prognostically relevant basal and classical pancreatic cancer subtypes and identifies plasma-inferred expression as a biomarker of response to enfortumab vedotin in metastatic bladder cancer. Together, these findings establish APEX as a biopsy-free approach for profiling tumor transcriptional states and extend liquid biopsy beyond genomic alterations to clinically relevant gene expression programs.

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