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May 7th, 2025
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TTCRC, Tata Medical Center, Kolkata
cancer biology
biorxiv

Insights into gallbladder cancer pathogenesis from a living organoid gallbladder cholangiocyte biorepository

Dutta, A.Open in Google Scholar•Chowdhury, N.Open in Google Scholar•Selvarajan, A. V.Open in Google Scholar•Banerjee, P.Open in Google Scholar•Kar, A.Open in Google Scholar•Chandra, S.Open in Google Scholar•Sunderam, U.Open in Google Scholar•Ganguli, D.Open in Google Scholar•Dutta, T.Open in Google Scholar•Basak, D.Open in Google Scholaret al.

Gallbladder cancer (GBC) while rare worldwide has a high prevalence in India. Pathogenesis is unclear and outcomes poor. Gallbladder cholangiocyte organoids (GCOs) or gallbladder carcinoma organoids (GBCOs) were developed and serially propagated from surgically resected gallbladder tissues with benign or malignant diseases, respectively. Patient derived organoids (PDOs) were derived from 15 normal; 58 inflamed; 12 xanthogranulomatous cholecystitis (XGC); 5 pre-invasive neoplasm and 13 invasive malignant gallbladder pathologies. Protocol optimisation achieved 58% (69/119) success in organoid generation and expansion. Organoids maintained tight junction integrity; P-gp pump and enzymatic activity; preserved tissue-specific gene and protein marker expression; histological features and genetic variations. Cryopreserved organoids from 62 patients with primary tissue and high-quality DNA, RNA and protein derivatives have been banked. In gene expression analyses of tissue, XGC samples clustered with malignant subtypes, separate from benign pathologies. Derived XGC organoids showed a similar clustering. Enriched hallmark pathways in XGC support neoplastic change through chronic inflammation. PDOs generated from different gallbladder pathologies are a promising model to investigate the pathogenesis of GBC.

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