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@ARTICLE{Blandino:294671,
      author       = {A. Blandino and D. Scherer and F. Boekstegers and T. B.
                      Rounge and H. Langseth and S. Roessler and K. Hveem and H.
                      Brenner$^*$ and S. Pechlivanis and M. Waldenberger and J.
                      Lorenzo Bermejo},
      title        = {{S}mall-{RNA} sequencing reveals potential serum biomarkers
                      for gallbladder cancer: {R}esults from a three-stage
                      collaborative study of large {E}uropean prospective
                      cohorts.},
      journal      = {European journal of cancer},
      volume       = {214},
      issn         = {0014-2964},
      address      = {Amsterdam [u.a.]},
      publisher    = {Elsevier},
      reportid     = {DKFZ-2024-02406},
      pages        = {115138},
      year         = {2025},
      note         = {Volume 214, January 2025, 115138},
      abstract     = {Gallbladder cancer (GBC) is an aggressive disease with
                      limited treatment options but high prevention potential. GBC
                      tumours take 10-20 years to develop, a timeframe that holds
                      potential for early detection. MicroRNAs (miRNAs) play a
                      central role in abnormal cell processes, and circulating
                      miRNAs may constitute valuable biomarkers of early disease.
                      We used microarray data to pre-select differentially
                      expressed miRNAs in formalin-fixed paraffin-embedded (FFPE)
                      gallbladder tissue samples (GBC n = 40, normal n = 8). We
                      then applied small-RNA sequencing to screen for miRNA
                      expression differences in serum samples from three European
                      prospective cohorts (n = 37 GBC case-control pairs), and
                      validated the most promising candidates in three independent
                      cohorts (n = 36 GBC case- control pairs). Statistical
                      analyses included robust linear regression, pathway and
                      meta-analysis, and examination of expression correlation
                      between miRNAs and target genes. MiR-4533 and miR-671-5p
                      were overexpressed in GBC tissue and serum samples, and
                      meta-analysis confirmed the overexpression of miR-4533 in
                      GBC serum samples from the prospective cohorts (p-value =
                      4.1×10-4), especially in individuals of female sex, under
                      63.5 years, or with a BMI below 26.2 kg/m2. Pathway and
                      correlation analyses revealed that miR-4533 targets SIPA1L2
                      in the Rap1 signalling pathway, and SIPA1L2 was
                      downregulated in GBC serum samples. Our study highlights the
                      advantage of integrating small-RNA sequencing results from
                      different types of samples and independent datasets, and the
                      need for international research collaborations to identify
                      and validate biomarkers for secondary prevention of rare
                      tumours such as GBC. The function of miR-4533 and its
                      interaction with SIPA1L2 in GBC development need to be
                      further investigated.},
      keywords     = {Gallbladder cancer (Other) / MicroRNAs (Other) / Molecular
                      phenotypes (Other) / Prospective serum samples (Other) /
                      Serum biomarkers (Other)},
      cin          = {C070 / HD01},
      ddc          = {610},
      cid          = {I:(DE-He78)C070-20160331 / I:(DE-He78)HD01-20160331},
      pnm          = {313 - Krebsrisikofaktoren und Prävention (POF4-313)},
      pid          = {G:(DE-HGF)POF4-313},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:39579640},
      doi          = {10.1016/j.ejca.2024.115138},
      url          = {https://inrepo02.dkfz.de/record/294671},
}