Small-RNA sequencing reveals potential serum biomarkers for gallbladder cancer: Results from a three-stage collaborative study of large European prospective cohorts.

Autor: Blandino A; Statistical Genetics Research Group, Institute of Medical Biometry, Heidelberg University, Heidelberg, Germany., Scherer D; Statistical Genetics Research Group, Institute of Medical Biometry, Heidelberg University, Heidelberg, Germany., Boekstegers F; Statistical Genetics Research Group, Institute of Medical Biometry, Heidelberg University, Heidelberg, Germany., Rounge TB; Department of Research, Cancer Registry of Norway, Norwegian Institute of Public Health, Oslo, Norway; Center for Bioinformatics, Department of Pharmacy, University of Oslo, Oslo, Norway., Langseth H; Department of Research, Cancer Registry of Norway, Norwegian Institute of Public Health, Oslo, Norway; Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK., Roessler S; Liver Cancer Center Heidelberg (LCCH), Heidelberg, Germany; Institute of Pathology, Heidelberg University Hospital, Heidelberg University, Heidelberg, Germany., Hveem K; HUNT Research Centre, Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway; HUNT Center for Molecular and Clinical Epidemiology, Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology), Trondheim, Norway; Department of Research, St Olav's Hospital, Trondheim, Norway., Brenner H; Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany; German Cancer Consortium, German Cancer Research Center, Heidelberg, Germany., Pechlivanis S; Institute for Asthma and Allergy Prevention, Helmoltz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany., Waldenberger M; Research Unit Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany; Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany., Lorenzo Bermejo J; Statistical Genetics Research Group, Institute of Medical Biometry, Heidelberg University, Heidelberg, Germany; Laboratory of Biostatistics for Precision Oncology, Institut de Cancérologie Strasbourg Europe, France. Electronic address: lorenzo@imbi.uni.heidelberg.de.
Jazyk: angličtina
Zdroj: European journal of cancer (Oxford, England : 1990) [Eur J Cancer] 2025 Jan; Vol. 214, pp. 115138. Date of Electronic Publication: 2024 Nov 20.
DOI: 10.1016/j.ejca.2024.115138
Abstrakt: 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/m 2 . 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.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE
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