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Integrated spatial morpho-transcriptomics predicts functional traits in pancreatic cancer.

Dennis Gong, Rachel Liu, Yi Cui

    Biorxiv : the Preprint Server for Biology
    |March 31, 2025
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    Summary

    Cell morphology analysis reveals new insights into pancreatic cancer. Distinct cell shapes and organization patterns in patient-derived models correlate with drug resistance and metastatic potential, aiding precision oncology.

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    Area of Science:

    • Oncology
    • Cell Biology
    • Genomics

    Background:

    • Patient-derived cell lines are crucial for identifying cancer biomarkers and therapeutic targets.
    • Characterization of cellular morphology in these models remains underexplored.
    • Understanding morphological properties can enhance the utility of in vitro models.

    Purpose of the Study:

    • To investigate the association between cell morphology and drug sensitivity, gene expression, and functional properties in human pancreatic adenocarcinoma (PDAC) cell lines.
    • To identify morphological changes indicative of drug resistance.
    • To explore the prognostic value of cell organization patterns in PDAC tissues.

    Main Methods:

    • Integrated live-cell imaging and spatial mRNA analysis.
    • Categorized PDAC cell lines into morphological and organizational subtypes.
    • Analyzed gene expression, drug sensitivity, and metastatic potential across subtypes.
    • Examined prognostic expression signatures in human PDAC tissues.

    Main Results:

    • Identified KRAS inhibitor-induced morphological changes specific to drug-resistant cells, correlating with gene expression.
    • Classified PDAC cell lines into distinct morphological and organizational subtypes.
    • Found significant differences in gene expression, therapeutic targeting, and metastatic potential among subtypes.
    • Discovered prognostic expression signatures linked to specific cancer cell organization patterns in tissues.

    Conclusions:

    • Cell morphology provides valuable information for understanding pancreatic adenocarcinoma biology.
    • Morphological and organizational subtypes of PDAC cell lines exhibit distinct molecular and functional characteristics.
    • Morphological profiling offers a rapid, cost-effective approach to enhance precision oncology using patient-derived models and tissues.