2026-04-17T03:27:52Zhttps://recercat.cat/oai/requestoai:recercat.cat:11351/144232026-04-03T00:54:15Zcom_2072_378070com_2072_378040col_2072_378092
RECERCAT
author
Langtry, Alberto
author
Rabadan, Raul
author
Alonso, Lola
author
Filip, Ioan
author
Sabroso-Lasa, Sergio
author
Moreno-Oya, Ane
author
Molero, Xavier
author
Balsells Valls, Joaquim
2026-04-03T00:54:15Z
2026-04-03T00:54:15Z
2026-04-01T12:49:44Z2026-04-01T12:49:44Z2025-11-28
https://hdl.handle.net/11351/14423
Prognosis; Pancreatic cancerPronòstic; Càncer de pàncreesPronóstico; Cáncer de páncreasPancreatic 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).
Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess
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
Deciphering the role of complement system genes in pancreatic cancer susceptibility and prognosis
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion