Deciphering the role of complement system genes in pancreatic cancer susceptibility and prognosis
Por:
Langtry, A, Rabadan, R, Alonso, L, Filip, I, Sabroso-Lasa, S, Moreno-Oya, A, Lawlor, R, Carrato, A, Alvarez-Gallego, R, Iglesias, M, Molero, X, Löhr, MJ, Michalski, CW, Perea, J, O'Rorke, M, Barberà, VM, Tardon, A, Farré, A, Muñoz-Bellvís, L, Crnogorac-Jurcevic, T, Domínguez-Muñoz, E, Gress, TM, Greenhalf, W, Sharp, L, Balsells, J, Costello, E, Kleeff, J, Kong, B, Mora, J, O'Driscoll, D, Scarpa, A, Ye, WM, Real, FX, de Maturana, EL, Malats, N, Gomez-Rubio, P, Molina-Montes, E, Márquez, M, Milne, R, Alfaro, A, Lobato, T, Estudillo, L, Beghelli, S, Cubillo, A, Hidalgo, M, Peinado, P, Salas, I, Pascual, JR, Earl, J, Caminoa, A, Guillén-Ponce, C, Rodríguez-Garrote, M, Longo-Muñoz, F, Ferreiro, R, Pachon, V, Vaz, MA, Muñoz, M, Ilzarbe, L, Alvarez-Urturi, C, Bessa, X, Bory, F, Márquez, L, Poves, I, Burdío, F, Grande, L, Gimeno, J, Guarner, L, Balcells, J, Salcedo, M, Merino, X, Esposito, I, Mota, C, Huang, JQ, Verbeke, C, Yu, JR, Loinaz, C, Rodríguez-Peralto, JL, Teijo, A, Peláez, P, Martín, M, Artigas, V, Guarner, C, Sancho, FJ, Concepcion, M, Cajal, TRY, Szafranska, J, Murray, L, Cantwell, M, Gallego, J, Barneo, L, Rodriguez-Suarez, M, Pazos, Y, Lozano, A, Luaces, M, Blanco-Antona, F, Manzano, JMS, Troncoso, MLG, de Matos, AO, Buchholz, M, Neesse, A, Kocher, HM, Bhattacharya, S, Abraham, AT, Ennis, D, Dowe, T, Radon, T
Publicada:
28 nov 2025
Resumen:
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.
Filiaciones:
Langtry, A:
Spanish Natl Canc Res Ctr CNIO, Genet & Mol Epidemiol Grp, Madrid, Spain
Rabadan, R:
Columbia Univ, Dept Syst Biol, New York, NY USA
Alonso, L:
Spanish Natl Canc Res Ctr CNIO, Genet & Mol Epidemiol Grp, Madrid, Spain
CIBERONC, Madrid, Spain
Filip, I:
Columbia Univ, Dept Syst Biol, New York, NY USA
Sabroso-Lasa, S:
Spanish Natl Canc Res Ctr CNIO, Genet & Mol Epidemiol Grp, Madrid, Spain
Moreno-Oya, A:
Spanish Natl Canc Res Ctr CNIO, Genet & Mol Epidemiol Grp, Madrid, Spain
CIBERONC, Madrid, Spain
Lawlor, R:
ARC Net Ctr Appl Res Canc, Dept Diagnost & Publ Hlth, Verona, Italy
Univ Verona, Dept Engn Innovat Med, Verona, Italy
Carrato, A:
CIBERONC, Madrid, Spain
Ramon & Cajal Univ Hosp, Dept Oncol, Madrid, Spain
Inst Ramon & Cajal Invest Sanitaria IRYCIS, Madrid, Spain
Alcala Univ, Madrid, Spain
Alvarez-Gallego, R:
Hosp Univ HM Sanchinarro, Inst Invest Sanitaria HM Hosp, HM CIOCC Madrid Ctr Integral Oncol Clara Campal, Madrid, Spain
Univ Camilo Jose Cela, Fac HM Ciencias Salud, Madrid, Spain
Iglesias, M:
CIBERONC, Madrid, Spain
Hosp Mar Parc Salut Mar, Dept Pathol, Barcelona, Spain
Molero, X:
Hosp Valle De Hebron, Dept Gastroenterol, Barcelona, Spain
Hosp Univ Arnau de Vilanova & Santa Maria, IRBLleida, UdL, Lleida, Spain
CIBEREHD, Madrid, Spain
Löhr, MJ:
Karolinska Inst, Gastroctr, Stockholm, Sweden
Univ Hosp, Stockholm, Sweden
Michalski, CW:
Tech Univ Munich, Dept Surg, Munich, Germany
Heidelberg Univ, Med Fac Heidelberg, Dept Gen Visceral & Transplantat Surg, Heidelberg, Germany
Perea, J:
Hosp 12 Octubre, Dept Surg, Madrid, Spain
Inst Biomed Res Salamanca, Salamanca, Spain
O'Rorke, M:
Queens Univ Belfast, Ctr Publ Hlth, Belfast, North Ireland
Univ Iowa, Coll Publ Hlth, Iowa City, IA USA
Barberà, VM:
Gen Univ Hosp Elche, Mol Genet Lab, Elche, Spain
Tardon, A:
Inst Univ Oncol Principado Asturias IUOPA, Dept Med, Oviedo, Spain
Inst Invest Sanitaria Principado Asturias ISPA, Oviedo, Spain
CIBERESP, Madrid, Spain
Farré, A:
Hosp Santa Creu & Sant Pau, Dept Gastroenterol, Barcelona, Spain
Muñoz-Bellvís, L:
CIBERONC, Madrid, Spain
Univ Salamanca, Hosp Univ Salamanca, Dept Surg, IBSAL, Salamanca, Spain
Crnogorac-Jurcevic, T:
Queen Mary Univ London, Barts Canc Inst, Ctr Canc Biomarkers & Biotherapeut, London, England
Domínguez-Muñoz, E:
Univ Clin Hosp Santiago de Compostela, Dept Gastroenterol, Santiago De Compostela, Spain
Gress, TM:
Univ Hosp Giessen & Marburg, Dept Gastroenterol, Marburg, Germany
Greenhalf, W:
Univ Liverpool, Dept Mol & Clin Canc Med, Liverpool, England
Sharp, L:
Univ Coll Cork, Natl Canc Registry Ireland, Cork, Ireland
Univ Coll Cork, HRB Clin Res Facil, Cork, Ireland
Newcastle Univ, Inst Hlth & Soc, Newcastle Upon Tyne, England
Balsells, J:
Hosp Valle De Hebron, Dept Surg, Barcelona, Spain
Costello, E:
Univ Liverpool, Dept Mol & Clin Canc Med, Liverpool, England
Kleeff, J:
Tech Univ Munich, Dept Surg, Munich, Germany
Martin Luther Univ Wittenber Halle Saale, Dept Visceral Vasc & Endocrine Surg, Halle An Der Saale, Germany
Kong, B:
Tech Univ Munich, Dept Surg, Munich, Germany
Heidelberg Univ, Med Fac Heidelberg, Dept Gen Visceral & Transplantat Surg, Heidelberg, Germany
Mora, J:
Hosp Santa Creu & Sant Pau, Dept Clin Biochem, Barcelona, Spain
O'Driscoll, D:
Univ Coll Cork, Natl Canc Registry Ireland, Cork, Ireland
Univ Coll Cork, HRB Clin Res Facil, Cork, Ireland
Scarpa, A:
ARC Net Ctr Appl Res Canc, Dept Diagnost & Publ Hlth, Verona, Italy
Univ Verona, Dept Engn Innovat Med, Verona, Italy
Ye, WM:
Karolinska Inst, Dept Med Epidemiol & Biostat, Stokholm, Sweden
Real, FX:
CIBERONC, Madrid, Spain
Spanish Natl Canc Res Ctr CNIO, Epithelial Carcinogenesis Grp, Madrid, Spain
Pompeu Fabra Univ, Barcelona, Spain
de Maturana, EL:
Spanish Natl Canc Res Ctr CNIO, Genet & Mol Epidemiol Grp, Madrid, Spain
CIBERONC, Madrid, Spain
Malats, N:
Spanish Natl Canc Res Ctr CNIO, Genet & Mol Epidemiol Grp, Madrid, Spain
CIBERONC, Madrid, Spain
Gomez-Rubio, P:
Spanish Natl Canc Res Ctr CNIO, Genet & Mol Epidemiol Grp, Madrid, Spain
Molina-Montes, E:
Spanish Natl Canc Res Ctr CNIO, Genet & Mol Epidemiol Grp, Madrid, Spain
Márquez, M:
Spanish Natl Canc Res Ctr CNIO, Genet & Mol Epidemiol Grp, Madrid, Spain
Milne, R:
Spanish Natl Canc Res Ctr CNIO, Genet & Mol Epidemiol Grp, Madrid, Spain
Alfaro, A:
Spanish Natl Canc Res Ctr CNIO, Genet & Mol Epidemiol Grp, Madrid, Spain
Lobato, T:
Spanish Natl Canc Res Ctr CNIO, Genet & Mol Epidemiol Grp, Madrid, Spain
Estudillo, L:
Spanish Natl Canc Res Ctr CNIO, Genet & Mol Epidemiol Grp, Madrid, Spain
Beghelli, S:
ARC Net Ctr Appl Res Canc, Dept Diagnost & Publ Hlth, Verona, Italy
Univ Verona, Dept Engn Innovat Med, Verona, Italy
Cubillo, A:
Hosp Univ HM Sanchinarro, Inst Invest Sanitaria HM Hosp, HM CIOCC Madrid Ctr Integral Oncol Clara Campal, Madrid, Spain
Univ Camilo Jose Cela, Fac HM Ciencias Salud, Madrid, Spain
Hidalgo, M:
Hosp Univ HM Sanchinarro, Inst Invest Sanitaria HM Hosp, HM CIOCC Madrid Ctr Integral Oncol Clara Campal, Madrid, Spain
Univ Camilo Jose Cela, Fac HM Ciencias Salud, Madrid, Spain
Peinado, P:
Hosp Univ HM Sanchinarro, Inst Invest Sanitaria HM Hosp, HM CIOCC Madrid Ctr Integral Oncol Clara Campal, Madrid, Spain
Univ Camilo Jose Cela, Fac HM Ciencias Salud, Madrid, Spain
Salas, I:
Hosp Univ HM Sanchinarro, Inst Invest Sanitaria HM Hosp, HM CIOCC Madrid Ctr Integral Oncol Clara Campal, Madrid, Spain
Univ Camilo Jose Cela, Fac HM Ciencias Salud, Madrid, Spain
Pascual, JR:
Hosp Univ HM Sanchinarro, Inst Invest Sanitaria HM Hosp, HM CIOCC Madrid Ctr Integral Oncol Clara Campal, Madrid, Spain
Univ Camilo Jose Cela, Fac HM Ciencias Salud, Madrid, Spain
Earl, J:
CIBERONC, Madrid, Spain
Ramon & Cajal Univ Hosp, Dept Oncol, Madrid, Spain
Inst Ramon & Cajal Invest Sanitaria IRYCIS, Madrid, Spain
Caminoa, A:
CIBERONC, Madrid, Spain
Ramon & Cajal Univ Hosp, Dept Oncol, Madrid, Spain
Inst Ramon & Cajal Invest Sanitaria IRYCIS, Madrid, Spain
Guillén-Ponce, C:
CIBERONC, Madrid, Spain
Ramon & Cajal Univ Hosp, Dept Oncol, Madrid, Spain
Inst Ramon & Cajal Invest Sanitaria IRYCIS, Madrid, Spain
Rodríguez-Garrote, M:
CIBERONC, Madrid, Spain
Ramon & Cajal Univ Hosp, Dept Oncol, Madrid, Spain
Inst Ramon & Cajal Invest Sanitaria IRYCIS, Madrid, Spain
Longo-Muñoz, F:
CIBERONC, Madrid, Spain
Ramon & Cajal Univ Hosp, Dept Oncol, Madrid, Spain
Inst Ramon & Cajal Invest Sanitaria IRYCIS, Madrid, Spain
Ferreiro, R:
CIBERONC, Madrid, Spain
Ramon & Cajal Univ Hosp, Dept Oncol, Madrid, Spain
Inst Ramon & Cajal Invest Sanitaria IRYCIS, Madrid, Spain
Pachon, V:
CIBERONC, Madrid, Spain
Ramon & Cajal Univ Hosp, Dept Oncol, Madrid, Spain
Inst Ramon & Cajal Invest Sanitaria IRYCIS, Madrid, Spain
Vaz, MA:
CIBERONC, Madrid, Spain
Ramon & Cajal Univ Hosp, Dept Oncol, Madrid, Spain
Inst Ramon & Cajal Invest Sanitaria IRYCIS, Madrid, Spain
Muñoz, M:
CIBERONC, Madrid, Spain
Ramon & Cajal Univ Hosp, Dept Oncol, Madrid, Spain
Inst Ramon & Cajal Invest Sanitaria IRYCIS, Madrid, Spain
Ilzarbe, L:
Hosp Mar Parc Salut Mar, Dept Pathol, Barcelona, Spain
Alvarez-Urturi, C:
Hosp Mar Parc Salut Mar, Dept Pathol, Barcelona, Spain
Bessa, X:
Hosp Mar Parc Salut Mar, Dept Pathol, Barcelona, Spain
Bory, F:
Hosp Mar Parc Salut Mar, Dept Pathol, Barcelona, Spain
Márquez, L:
Hosp Mar Parc Salut Mar, Dept Pathol, Barcelona, Spain
Poves, I:
Hosp Mar Parc Salut Mar, Dept Pathol, Barcelona, Spain
Burdío, F:
Hosp Mar Parc Salut Mar, Dept Pathol, Barcelona, Spain
Grande, L:
Hosp Mar Parc Salut Mar, Dept Pathol, Barcelona, Spain
Gimeno, J:
Hosp Mar Parc Salut Mar, Dept Pathol, Barcelona, Spain
Guarner, L:
Hosp Valle De Hebron, Dept Gastroenterol, Barcelona, Spain
Balcells, J:
Hosp Valle De Hebron, Dept Gastroenterol, Barcelona, Spain
Salcedo, M:
Hosp Valle De Hebron, Dept Gastroenterol, Barcelona, Spain
Merino, X:
Hosp Valle De Hebron, Dept Gastroenterol, Barcelona, Spain
Esposito, I:
Tech Univ Munich, Dept Surg, Munich, Germany
Mota, C:
Tech Univ Munich, Dept Surg, Munich, Germany
Huang, JQ:
Karolinska Inst, Gastroctr, Stockholm, Sweden
Univ Hosp, Stockholm, Sweden
Verbeke, C:
Karolinska Inst, Gastroctr, Stockholm, Sweden
Univ Hosp, Stockholm, Sweden
Yu, JR:
Karolinska Inst, Dept Med Epidemiol & Biostat, Stokholm, Sweden
Loinaz, C:
Hosp 12 Octubre, Dept Surg, Madrid, Spain
Rodríguez-Peralto, JL:
Hosp 12 Octubre, Dept Surg, Madrid, Spain
Teijo, A:
Hosp 12 Octubre, Dept Surg, Madrid, Spain
Peláez, P:
Hosp 12 Octubre, Dept Surg, Madrid, Spain
Martín, M:
Hosp Santa Creu & Sant Pau, Dept Gastroenterol, Barcelona, Spain
Artigas, V:
Hosp Santa Creu & Sant Pau, Dept Gastroenterol, Barcelona, Spain
Guarner, C:
Hosp Santa Creu & Sant Pau, Dept Gastroenterol, Barcelona, Spain
Sancho, FJ:
Hosp Santa Creu & Sant Pau, Dept Gastroenterol, Barcelona, Spain
Concepcion, M:
Hosp Santa Creu & Sant Pau, Dept Gastroenterol, Barcelona, Spain
Cajal, TRY:
Hosp Santa Creu & Sant Pau, Dept Gastroenterol, Barcelona, Spain
Szafranska, J:
Hosp Santa Creu & Sant Pau, Dept Gastroenterol, Barcelona, Spain
Murray, L:
Queens Univ Belfast, Ctr Publ Hlth, Belfast, North Ireland
Cantwell, M:
Queens Univ Belfast, Ctr Publ Hlth, Belfast, North Ireland
Gallego, J:
Gen Univ Hosp Elche, Mol Genet Lab, Elche, Spain
Barneo, L:
Inst Univ Oncol Principado Asturias IUOPA, Dept Med, Oviedo, Spain
Rodriguez-Suarez, M:
Inst Univ Oncol Principado Asturias IUOPA, Dept Med, Oviedo, Spain
Pazos, Y:
Univ Clin Hosp Santiago de Compostela, Dept Gastroenterol, Santiago De Compostela, Spain
Lozano, A:
Univ Clin Hosp Santiago de Compostela, Dept Gastroenterol, Santiago De Compostela, Spain
Luaces, M:
Univ Clin Hosp Santiago de Compostela, Dept Gastroenterol, Santiago De Compostela, Spain
Blanco-Antona, F:
CIBERONC, Madrid, Spain
Univ Salamanca, Hosp Univ Salamanca, Dept Surg, IBSAL, Salamanca, Spain
Manzano, JMS:
CIBERONC, Madrid, Spain
Univ Salamanca, Hosp Univ Salamanca, Dept Surg, IBSAL, Salamanca, Spain
Troncoso, MLG:
CIBERONC, Madrid, Spain
Univ Salamanca, Hosp Univ Salamanca, Dept Surg, IBSAL, Salamanca, Spain
de Matos, AO:
CIBERONC, Madrid, Spain
Univ Salamanca, Hosp Univ Salamanca, Dept Surg, IBSAL, Salamanca, Spain
Buchholz, M:
Univ Hosp Giessen & Marburg, Dept Gastroenterol, Marburg, Germany
Neesse, A:
Univ Hosp Giessen & Marburg, Dept Gastroenterol, Marburg, Germany
Kocher, HM:
Queen Mary Univ London, Barts Canc Inst, Ctr Canc Biomarkers & Biotherapeut, London, England
Bhattacharya, S:
Queen Mary Univ London, Barts Canc Inst, Ctr Canc Biomarkers & Biotherapeut, London, England
Abraham, AT:
Queen Mary Univ London, Barts Canc Inst, Ctr Canc Biomarkers & Biotherapeut, London, England
Ennis, D:
Queen Mary Univ London, Barts Canc Inst, Ctr Canc Biomarkers & Biotherapeut, London, England
Dowe, T:
Queen Mary Univ London, Barts Canc Inst, Ctr Canc Biomarkers & Biotherapeut, London, England
Radon, T:
Queen Mary Univ London, Barts Canc Inst, Ctr Canc Biomarkers & Biotherapeut, London, England
Green Submitted, gold
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