Integrated spatial morpho-transcriptomics predicts functional traits in pancreatic cancer
Menée à l'aide de lignées cellulaires dérivées d'adénocarcinomes humains du pancréas et menée à l'aide de données morpho-transcriptomiques spatiales portant sur des échantillons tumoraux, cette étude met en évidence une corrélation entre des évolutions d'expression de gènes de cellules cancéreuses, des modifications morphologiques et la réponse thérapeutique
Analyses of patient-derived cell lines have greatly enhanced discovery of molecular biomarkers and therapeutic targets. However, characterization of cellular morphological properties is limited. We studied cell morphologies of human pancreatic adenocarcinoma (PDAC) cell lines and their associations with drug sensitivity, gene expression, and functional properties. By integrating live cell and spatial messenger RNA imaging, we identified KRAS inhibitor–induced morphological changes specific for drug-resistant cells that correlated with gene expression changes. We then categorized a large panel of patient-derived PDAC cell lines into morphological and organizational subtypes and found differences in gene expression, therapeutic targeting potential, and metastatic proclivity. Patterns of cancer cell organization in human PDAC tissues stratified distinct gene expression signatures with clinical significance. In summary, we highlight the potential of cell morphological information in rapid, cost-effective assays to aid precision oncology efforts leveraging patient-derived in vitro models and tissues. Changes in pancreatic cancer cell shape are correlated with treatment response and are associated with cellular functions.
Science Advances , résumé, 2025