2026-04-17T11:28:02Zhttps://recercat.cat/oai/request

oai:recercat.cat:11351/144232026-04-03T00:54:15Zcom_2072_378070com_2072_378040col_2072_378092

Deciphering the role of complement system genes in pancreatic cancer susceptibility and prognosis Langtry, Alberto Rabadan, Raul Alonso, Lola Filip, Ioan Sabroso-Lasa, Sergio Moreno-Oya, Ane Molero, Xavier Balsells Valls, Joaquim Pàncrees - Càncer - Prognosi Pàncrees - Càncer - Aspectes genètics ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Diagnosis::Prognosis DISEASES::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Pancreatic Neoplasms Other subheadings::Other subheadings::Other subheadings::/genetics DISEASES::Neoplasms::Neoplasms::Neoplasms::Neoplasms by Site::Neoplasms::Neoplasms by Site::Endocrine Gland Neoplasms::Pancreatic Neoplasms::Carcinoma, Pancreatic Ductal TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::diagnóstico::pronóstico ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias del sistema digestivo::neoplasias pancreáticas Otros calificadores::Otros calificadores::Otros calificadores::/genética ENFERMEDADES::neoplasias::neoplasias::neoplasias::neoplasias por localización::neoplasias::neoplasias por localización::neoplasias de las glándulas endocrinas::neoplasias pancreáticas::carcinoma ductal pancreático Prognosis; Pancreatic cancer Pronòstic; Càncer de pàncrees Pronóstico; Cáncer de páncreas 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. 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). 2026-04-03T00:54:15Z 2026-04-03T00:54:15Z 2026-04-03T00:54:15Z 2026-04-01T12:49:44Z 2026-04-01T12:49:44Z 2025-11-28 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion https://hdl.handle.net/11351/14423 Nature Communications;16 https://doi.org/10.1038/s41467-025-65811-y Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess Nature Portfolio Scientia