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Mast cells and histamine in cholangiocarcinoma: exploring overlooked avenues for enhanced patient management
  1. Luca Fabris1,2,
  2. Jonathan Pol3,4
  1. 1Department of Medicine (DIMED), 1st Clinical Medicine Unit, University of Padova, Padova, Italy
  2. 2Department of Internal Medicine, Digestive Disease Section, Yale University, New Haven, CT, USA
  3. 3Centre de Recherche des Cordeliers Centre de Recherche des Cordeliers, Equipe labellisée par la Ligue contre le cancer, Inserm U1138, Université Paris Cité, Sorbonne Université, Paris, France
  4. 4Metabolomics and Cell Biology Platforms, Gustave Roussy Institute, Villejuif, France
  1. Correspondence to Dr Luca Fabris, Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy; luca.fabris{at}

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In the realm of cholangiocarcinoma (CCA), a malignancy often presenting with biliary stenosis, the clinical need to re-establish duct patency offers a unique opportunity to profile bile content, facilitating the identification of potential diagnostic and prognostic biomarkers. Various studies have explored the significance of biochemically distinct molecules in the bile of patients with CCA by comparing with healthy or unrelated biliary disorder controls. These investigations revealed promising candidates for diagnostic purposes, encompassing proteins (eg, clusterin, soluble B7-H4, alpha-1 antitrypsin, heat shock proteins HSP27 and HSP70), cell-free nucleic acids (eg, miR-9, RNU2-1f, miR-30d-5p) or again metabolites (eg, phosphatidylcholine, taurine/glycine-conjugated bile acids).1 2 Despite these advancements, the repertoire of bile biomarkers for prognostication remains relatively limited.

An interesting bile biomarker with implications for prognosis in CCA is fibroblast growth factor 7 (FGF7).3 Research led by Zengli Liu and colleagues demonstrated that FGF7 was upregulated in both the bile and serum of patients with CCA and was associated with poor prognosis. The mechanistic underpinnings revealed that the FGF7–fibroblast growth factor receptor 2 (FGFR2) axis, driven by the transcription factor sry-box containing gene 9 (SOX9), played a crucial role in promoting CCA proliferation in an autocrine fashion. Moreover, this axis was implicated in the reduced sensitivity to the FGFR inhibitor pemigatinib.3

By focusing on the complex CCA tumour microenvironment (TME), a complementary study by Xu’s group, recently published in Gut, pointed out histamine (HA) as another meaningful bile biomarker, which …

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  • Contributors The authors are responsible for the full content.

  • Funding JP is supported by the SIRIC Cancer Research and Personalized Medicine (CARPEM), Multi-Organism Institute (ITMO) Aviesan Cancer (National Alliance for Life Sciences and Health), Institut National du Cancer (INCa), Agence Nationale de la Recherche sur le Sida et les Hépatites (ANRS) and Fondation pour la Recherche Médicale (FRM). LF is supported by PRIN (2022AHM4AA).

  • Competing interests None declared.

  • Provenance and peer review Commissioned; internally peer reviewed.

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