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However, the extremely low abundance of tumor secretome components remains a major limitation for reliable detection. Here, we introduce an AI-driven imaging framework that leverages chromatin-based cellular fingerprints as functional biosensors to detect cancer-associated blood-derived secretome signals. As a proof of concept, we demonstrate that human stromal fibroblasts exhibit a higher signal-to-noise ratio for detecting prostate cancer-derived secretomes isolated from whole blood compared with immune cells. Notably, aged fibroblasts display enhanced sensitivity relative to their young counterparts and T cells. To achieve a fully integrated sample-to-sensing workflow, we combined this imaging approach with a micropillar-guided secretome\/plasma isolation platform coupled to an on-chip cell-culture chamber, enabling rapid exposure of sensor cells to tumor-derived secretome factors. Together, our results establish a proof-of-concept exploratory study demonstrating the feasibility of chromatin-based functional biosensing of cancer-associated blood-derived secretome signals.<\/jats:p>","DOI":"10.1038\/s41598-026-58794-3","type":"journal-article","created":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T21:53:33Z","timestamp":1782770013000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Chromatin biomarkers reveal the fingerprints of cancer-associated secretomes isolated by a micropillar-guided platform"],"prefix":"10.1038","volume":"16","author":[{"given":"Zeynep","family":"Karavelioglu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonard","family":"Piroska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celestino","family":"Padeste","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G. 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