dc.contributor
Institut Català de la Salut
dc.contributor
[Langtry A, Sabroso-Lasa S] Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Center (CNIO), Madrid, Spain. [Rabadan R, Filip I] Department of Systems Biology, Columbia University, New York, NY, USA. [Alonso L, Moreno-Oya A] Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Center (CNIO), Madrid, Spain. CIBERONC, Madrid, Spain. [Molero X] S Servei d'Aparell Digestiu, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Hospitals Universitaris Arnau de Vilanova i Santa Maria, IRBLleida, UdL, Lleida, Spain. CIBEREHD, Madrid, Spain. [Balsells J] Servei de Cirurgia Hepatobiliopancreàtica i Trasplantaments, Vall d’Hebron Hospital Universitari, Barcelona, Spain
dc.contributor
Vall d'Hebron Barcelona Hospital Campus
dc.contributor.author
Langtry, Alberto
dc.contributor.author
Rabadan, Raul
dc.contributor.author
Alonso, Lola
dc.contributor.author
Filip, Ioan
dc.contributor.author
Sabroso-Lasa, Sergio
dc.contributor.author
Moreno-Oya, Ane
dc.contributor.author
Molero, Xavier
dc.contributor.author
Balsells Valls, Joaquim
dc.date.accessioned
2026-04-03T00:54:15Z
dc.date.available
2026-04-03T00:54:15Z
dc.date.issued
2026-04-01T12:49:44Z
dc.date.issued
2026-04-01T12:49:44Z
dc.date.issued
2025-11-28
dc.identifier
Langtry A, Rabadan R, Alonso L, Filip I, Sabroso-Lasa S, Moreno-Oya A, et al. Deciphering the role of complement system genes in pancreatic cancer susceptibility and prognosis. Nat Commun. 2025 Nov 28;16:10769.
dc.identifier
http://hdl.handle.net/11351/14423
dc.identifier
10.1038/s41467-025-65811-y
dc.identifier
001627854600033
dc.identifier.uri
https://hdl.handle.net/11351/14423
dc.description.abstract
Prognosis; Pancreatic cancer
dc.description.abstract
Pronòstic; Càncer de pàncrees
dc.description.abstract
Pronóstico; Cáncer de páncreas
dc.description.abstract
Pancreatic ductal adenocarcinoma (PDAC) genetic susceptibility is partially identified. The complement system (CS) influences carcinogenesis and participates in immunological defense and homeostasis; however, its role in PDAC genetic susceptibility and prognosis is underexplored. The association of SNPs within 111 CS-related genes with PDAC risk is assessed in the PanGenEU study and validated in the UKBiobank. We investigate the association between the CS-related gene variation and PDAC risk, followed by an in-depth functional in silico study using TCGA and ICGC data. We assess whether CS-related genes are associated with prognosis at the germline and somatic levels. We investigate the immune infiltration of PDAC tumors according to their transcriptomic profile. Genetic variation in FCN1 and PLAT is significantly associated with PDAC risk. PDAC patients with elevated expression of IGHG3, IGKC, IGHM, F2R, F2RL2, CFI, A2M, or C4A display improved survival and higher infiltration of CD8+, B cells, and Th1 cells. Individuals with high expression levels of either FGA, SERPINE1, FGG, or F3 exhibit poorer survival, higher infiltration of Tregs, and lower infiltration of CD8+ cells. Results from this study suggest that CS-related genes play a role in PDAC genetic susceptibility and survival through specific immune cell infiltration.
dc.description.abstract
The work was partially supported by Fondo de Investigaciones Sanitarias (FIS), Instituto de Salud Carlos III, Spain (#PI061614, #PI11/01542, #PI0902102, #PI12/01635, #PI12/00815, #PI15/01573, #PI18/01347, #PI21/00495); Ministerio de Ciencia, Innovación y Universidades, Madrid, Spain (#RTI2018-101071-B-I00 and #PID2021-128125OB-I00); Red Temática de Investigación Cooperativa en Cáncer, Spain (#RD12/0036/0034, #RD12/0036/0050, #RD12/0036/0073); Fundación Científica de la AECC, Spain; European Cooperation in Science and Technology - COST Action #BM1204: EUPancreas. EU-6FP Integrated Project (#018771-MOLDIAG-PACA), EU-FP7-HEALTH (#259737-CANCERALIA, #256974-EPC-TM-Net); Associazione Italiana Ricerca sul Cancro (#12182); Cancer Focus Northern Ireland and Department for Employment and Learning; and ALF (#SLL20130022), Sweden; Pancreatic Cancer Collective (PCC): Lustgarten Foundation & Stand-Up to Cancer, USA (SU2C #6179).
dc.format
application/pdf
dc.publisher
Nature Portfolio
dc.relation
Nature Communications;16
dc.relation
https://doi.org/10.1038/s41467-025-65811-y
dc.rights
Attribution-NonCommercial-NoDerivatives 4.0 International
dc.rights
http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights
info:eu-repo/semantics/openAccess
dc.subject
Pàncrees - Càncer - Prognosi
dc.subject
Pàncrees - Càncer - Aspectes genètics
dc.subject
ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Diagnosis::Prognosis
dc.subject
DISEASES::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Pancreatic Neoplasms
dc.subject
Other subheadings::Other subheadings::Other subheadings::/genetics
dc.subject
DISEASES::Neoplasms::Neoplasms::Neoplasms::Neoplasms by Site::Neoplasms::Neoplasms by Site::Endocrine Gland Neoplasms::Pancreatic Neoplasms::Carcinoma, Pancreatic Ductal
dc.subject
TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::diagnóstico::pronóstico
dc.subject
ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias del sistema digestivo::neoplasias pancreáticas
dc.subject
Otros calificadores::Otros calificadores::Otros calificadores::/genética
dc.subject
ENFERMEDADES::neoplasias::neoplasias::neoplasias::neoplasias por localización::neoplasias::neoplasias por localización::neoplasias de las glándulas endocrinas::neoplasias pancreáticas::carcinoma ductal pancreático
dc.title
Deciphering the role of complement system genes in pancreatic cancer susceptibility and prognosis
dc.type
info:eu-repo/semantics/article
dc.type
info:eu-repo/semantics/publishedVersion
