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Deciphering the role of complement system genes in pancreatic cancer susceptibility and prognosis

Author

Listed:
  • Alberto Langtry

    (Spanish National Cancer Research Center (CNIO), Genetic and Molecular Epidemiology Group)

  • Raul Rabadan

    (Columbia University, Department of Systems Biology)

  • Lola Alonso

    (Spanish National Cancer Research Center (CNIO), Genetic and Molecular Epidemiology Group
    CIBERONC)

  • Ioan Filip

    (Columbia University, Department of Systems Biology)

  • Sergio Sabroso-Lasa

    (Spanish National Cancer Research Center (CNIO), Genetic and Molecular Epidemiology Group)

  • Ane Moreno-Oya

    (Spanish National Cancer Research Center (CNIO), Genetic and Molecular Epidemiology Group
    CIBERONC)

  • Rita Lawlor

    (Department of Diagnostics and Public Health, ARC-Net Center for Applied Research on Cancer
    University of Verona, Department of Engineering for Innovation Medicine)

  • Alfredo Carrato

    (CIBERONC
    Ramón y Cajal University Hospital, Department of Oncology
    and CIBERONC, Instituto Ramón y Cajal de investigación sanitaria (IRYCIS), Madrid
    Alcala University)

  • Rafael Alvarez-Gallego

    (HM CIOCC Madrid (Centro Integral Oncológico Clara Campal). Hospital Universitario HM Sanchinarro. Instituto de Investigación Sanitaria HM Hospitales
    Facultad HM de Ciencias de la Salud de la Universidad Camilo José Cela)

  • Mar Iglesias

    (CIBERONC
    Hospital del Mar—Parc de Salut Mar, Department of Pathology)

  • Xavier Molero

    (Hospital Vall Hebron, Department of Gastroenterology
    UdL, Hospitals Universitaris Arnau de Vilanova i Santa Maria, IRBLleida
    CIBEREHD)

  • Matthias J. Löhr

    (Karolinska Institutet and University Hospital, Gastrocentrum)

  • Christoph W. Michalski

    (Technical University of Munich, Department of Surgery
    University Heidelberg, Department of General, Visceral and Transplantation Surgery, Medical Faculty Heidelberg)

  • José Perea

    (Hospital 12 de Octubre, Department of Surgery
    Institute of Biomedical Research of Salamanca)

  • Michael O’Rorke

    (Queen’s University Belfast, Centre for Public Health, Belfast
    The University of Iowa, College of Public Health)

  • Victor M. Barberà

    (General University Hospital of Elche, Molecular Genetics Laboratory)

  • Adonina Tardón

    (Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Department of Medicine
    Instituto de Investigación Sanitaria del Principado de Asturias (ISPA)
    CIBERESP)

  • Antoni Farré

    (Hospital de la Santa Creu i Sant Pau, Department of Gastroenterology)

  • Luís Muñoz-Bellvís

    (Salamanca; and CIBERONC, Department of Surgery, Hospital Universitario de Salamanca – IBSAL, Universidad de Salamanca)

  • Tatjana Crnogorac-Jurcevic

    (Queen Mary University of London, Barts Cancer Institute, Centre for Cancer Biomarkers and Biotherapeutics)

  • Enrique Domínguez-Muñoz

    (University Clinical Hospital of Santiago de Compostela, Department of Gastroenterology)

  • Thomas M. Gress

    (University Hospital of Giessen and Marburg, Department of Gastroenterology)

  • William Greenhalf

    (University of Liverpool, Department of Molecular and Clinical Cancer Medicine)

  • Linda Sharp

    (University College Cork, National Cancer Registry Ireland and HRB Clinical Research Facility
    Institute of Health & Society, Newcastle University)

  • Joaquim Balsells

    (Hospital Vall Hebron, Department of Surgery)

  • Eithne Costello

    (University of Liverpool, Department of Molecular and Clinical Cancer Medicine)

  • Jörg Kleeff

    (Technical University of Munich, Department of Surgery
    Martin-Luther-University Wittenber-Halle (Saale), Department of Visceral, Vascular and Endocrine Surgery)

  • Bo Kong

    (Technical University of Munich, Department of Surgery
    University Heidelberg, Department of General, Visceral and Transplantation Surgery, Medical Faculty Heidelberg)

  • Josefina Mora

    (Hospital de la Santa Creu i Sant Pau, Department of Clinical Biochemistry)

  • Damian O’Driscoll

    (University College Cork, National Cancer Registry Ireland and HRB Clinical Research Facility)

  • Aldo Scarpa

    (Department of Diagnostics and Public Health, ARC-Net Center for Applied Research on Cancer
    University of Verona, Department of Engineering for Innovation Medicine)

  • Weimin Ye

    (Karolinska Institutet, Department of Medical Epidemiology and Biostatistics)

  • Francisco X. Real

    (CIBERONC
    Spanish National Cancer Research Center (CNIO), Epithelial Carcinogenesis Group
    Pompeu Fabra University)

  • Evangelina López de Maturana

    (Spanish National Cancer Research Center (CNIO), Genetic and Molecular Epidemiology Group
    CIBERONC)

  • Núria Malats

    (Spanish National Cancer Research Center (CNIO), Genetic and Molecular Epidemiology Group
    CIBERONC)

  • Alberto Langtry

    (Spanish National Cancer Research Center (CNIO), Genetic and Molecular Epidemiology Group)

  • Lola Alonso

    (Spanish National Cancer Research Center (CNIO), Genetic and Molecular Epidemiology Group
    CIBERONC)

  • Sergio Sabroso-Lasa

    (Spanish National Cancer Research Center (CNIO), Genetic and Molecular Epidemiology Group)

  • Ane Moreno-Oya

    (Spanish National Cancer Research Center (CNIO), Genetic and Molecular Epidemiology Group
    CIBERONC)

  • Paulina Gómez-Rubio

    (Spanish National Cancer Research Center (CNIO), Genetic and Molecular Epidemiology Group)

  • Esther Molina-Montes

    (Spanish National Cancer Research Center (CNIO), Genetic and Molecular Epidemiology Group)

  • Mirari Márquez

    (Spanish National Cancer Research Center (CNIO), Genetic and Molecular Epidemiology Group)

  • Roger Milne

    (Spanish National Cancer Research Center (CNIO), Genetic and Molecular Epidemiology Group)

  • Ana Alfaro

    (Spanish National Cancer Research Center (CNIO), Genetic and Molecular Epidemiology Group)

  • Tania Lobato

    (Spanish National Cancer Research Center (CNIO), Genetic and Molecular Epidemiology Group)

  • Lidia Estudillo

    (Spanish National Cancer Research Center (CNIO), Genetic and Molecular Epidemiology Group)

  • Francisco X. Real

    (CIBERONC
    Spanish National Cancer Research Center (CNIO), Epithelial Carcinogenesis Group
    Pompeu Fabra University)

  • Núria Malats

    (Spanish National Cancer Research Center (CNIO), Genetic and Molecular Epidemiology Group
    CIBERONC)

  • Aldo Scarpa

    (Department of Diagnostics and Public Health, ARC-Net Center for Applied Research on Cancer
    University of Verona, Department of Engineering for Innovation Medicine)

  • Rita Lawlor

    (Department of Diagnostics and Public Health, ARC-Net Center for Applied Research on Cancer
    University of Verona, Department of Engineering for Innovation Medicine)

  • Stefania Beghelli

    (Department of Diagnostics and Public Health, ARC-Net Center for Applied Research on Cancer
    University of Verona, Department of Engineering for Innovation Medicine)

  • Rafael Alvarez-Gallego

    (HM CIOCC Madrid (Centro Integral Oncológico Clara Campal). Hospital Universitario HM Sanchinarro. Instituto de Investigación Sanitaria HM Hospitales
    Facultad HM de Ciencias de la Salud de la Universidad Camilo José Cela)

  • Antonio Cubillo

    (HM CIOCC Madrid (Centro Integral Oncológico Clara Campal). Hospital Universitario HM Sanchinarro. Instituto de Investigación Sanitaria HM Hospitales
    Facultad HM de Ciencias de la Salud de la Universidad Camilo José Cela)

  • Manuel Hidalgo

    (HM CIOCC Madrid (Centro Integral Oncológico Clara Campal). Hospital Universitario HM Sanchinarro. Instituto de Investigación Sanitaria HM Hospitales
    Facultad HM de Ciencias de la Salud de la Universidad Camilo José Cela)

  • Paloma Peinado

    (HM CIOCC Madrid (Centro Integral Oncológico Clara Campal). Hospital Universitario HM Sanchinarro. Instituto de Investigación Sanitaria HM Hospitales
    Facultad HM de Ciencias de la Salud de la Universidad Camilo José Cela)

  • Isabel Salas

    (HM CIOCC Madrid (Centro Integral Oncológico Clara Campal). Hospital Universitario HM Sanchinarro. Instituto de Investigación Sanitaria HM Hospitales
    Facultad HM de Ciencias de la Salud de la Universidad Camilo José Cela)

  • Jesús Rodríguez Pascual

    (HM CIOCC Madrid (Centro Integral Oncológico Clara Campal). Hospital Universitario HM Sanchinarro. Instituto de Investigación Sanitaria HM Hospitales
    Facultad HM de Ciencias de la Salud de la Universidad Camilo José Cela)

  • Alfredo Carrato

    (CIBERONC
    Ramón y Cajal University Hospital, Department of Oncology
    and CIBERONC, Instituto Ramón y Cajal de investigación sanitaria (IRYCIS), Madrid
    Alcala University)

  • Julie Earl

    (Ramón y Cajal University Hospital, Department of Oncology
    and CIBERONC, Instituto Ramón y Cajal de investigación sanitaria (IRYCIS), Madrid)

  • Alejandra Caminoa

    (Ramón y Cajal University Hospital, Department of Oncology
    and CIBERONC, Instituto Ramón y Cajal de investigación sanitaria (IRYCIS), Madrid)

  • Carmen Guillén-Ponce

    (Ramón y Cajal University Hospital, Department of Oncology
    and CIBERONC, Instituto Ramón y Cajal de investigación sanitaria (IRYCIS), Madrid)

  • Mercedes Rodríguez-Garrote

    (Ramón y Cajal University Hospital, Department of Oncology
    and CIBERONC, Instituto Ramón y Cajal de investigación sanitaria (IRYCIS), Madrid)

  • Federico Longo-Muñoz

    (Ramón y Cajal University Hospital, Department of Oncology
    and CIBERONC, Instituto Ramón y Cajal de investigación sanitaria (IRYCIS), Madrid)

  • Reyes Ferreiro

    (Ramón y Cajal University Hospital, Department of Oncology
    and CIBERONC, Instituto Ramón y Cajal de investigación sanitaria (IRYCIS), Madrid)

  • Vanessa Pachón

    (Ramón y Cajal University Hospital, Department of Oncology
    and CIBERONC, Instituto Ramón y Cajal de investigación sanitaria (IRYCIS), Madrid)

  • M. Ángeles Vaz

    (Ramón y Cajal University Hospital, Department of Oncology
    and CIBERONC, Instituto Ramón y Cajal de investigación sanitaria (IRYCIS), Madrid)

  • María Muñoz

    (Ramón y Cajal University Hospital, Department of Oncology
    and CIBERONC, Instituto Ramón y Cajal de investigación sanitaria (IRYCIS), Madrid)

  • Mar Iglesias

    (CIBERONC
    Hospital del Mar—Parc de Salut Mar, Department of Pathology)

  • Lucas Ilzarbe

    (Hospital del Mar—Parc de Salut Mar, Department of Pathology)

  • Cristina Álvarez-Urturi

    (Hospital del Mar—Parc de Salut Mar, Department of Pathology)

  • Xavier Bessa

    (Hospital del Mar—Parc de Salut Mar, Department of Pathology)

  • Felipe Bory

    (Hospital del Mar—Parc de Salut Mar, Department of Pathology)

  • Lucía Márquez

    (Hospital del Mar—Parc de Salut Mar, Department of Pathology)

  • Ignasi Poves

    (Hospital del Mar—Parc de Salut Mar, Department of Pathology)

  • Fernando Burdío

    (Hospital del Mar—Parc de Salut Mar, Department of Pathology)

  • Luis Grande

    (Hospital del Mar—Parc de Salut Mar, Department of Pathology)

  • Javier Gimeno

    (Hospital del Mar—Parc de Salut Mar, Department of Pathology)

  • Xavier Molero

    (Hospital Vall Hebron, Department of Gastroenterology
    UdL, Hospitals Universitaris Arnau de Vilanova i Santa Maria, IRBLleida
    CIBEREHD)

  • Luisa Guarner

    (Hospital Vall Hebron, Department of Gastroenterology)

  • Joaquín Balcells

    (Hospital Vall Hebron, Department of Gastroenterology)

  • Mayte Salcedo

    (Hospital Vall Hebron, Department of Gastroenterology)

  • Xavier Merino

    (Hospital Vall Hebron, Department of Gastroenterology)

  • Christoph W. Michalski

    (Technical University of Munich, Department of Surgery
    University Heidelberg, Department of General, Visceral and Transplantation Surgery, Medical Faculty Heidelberg)

  • Irene Esposito

    (Technical University of Munich, Department of Surgery)

  • Jörg Kleeff

    (Technical University of Munich, Department of Surgery
    Martin-Luther-University Wittenber-Halle (Saale), Department of Visceral, Vascular and Endocrine Surgery)

  • Bo Kong

    (Technical University of Munich, Department of Surgery
    University Heidelberg, Department of General, Visceral and Transplantation Surgery, Medical Faculty Heidelberg)

  • Carmen Mota

    (Technical University of Munich, Department of Surgery)

  • Matthias J. Löhr

    (Karolinska Institutet and University Hospital, Gastrocentrum)

  • Jiaqui Huang

    (Karolinska Institutet and University Hospital, Gastrocentrum)

  • Caroline Verbeke

    (Karolinska Institutet and University Hospital, Gastrocentrum)

  • Weimin Ye

    (Karolinska Institutet, Department of Medical Epidemiology and Biostatistics)

  • Jingru Yu

    (Karolinska Institutet, Department of Medical Epidemiology and Biostatistics)

  • Carmelo Loinaz

    (Hospital 12 de Octubre, Department of Surgery)

  • José Perea

    (Hospital 12 de Octubre, Department of Surgery
    Institute of Biomedical Research of Salamanca)

  • José Luis Rodríguez-Peralto

    (Hospital 12 de Octubre, Department of Surgery)

  • Ana Teijo

    (Hospital 12 de Octubre, Department of Surgery)

  • Pablo Peláez

    (Hospital 12 de Octubre, Department of Surgery)

  • Antoni Farré

    (Hospital de la Santa Creu i Sant Pau, Department of Gastroenterology)

  • Josefina Mora

    (Hospital de la Santa Creu i Sant Pau, Department of Gastroenterology)

  • Marta Martín

    (Hospital de la Santa Creu i Sant Pau, Department of Gastroenterology)

  • Vicenç Artigas

    (Hospital de la Santa Creu i Sant Pau, Department of Gastroenterology)

  • Carlos Guarner

    (Hospital de la Santa Creu i Sant Pau, Department of Gastroenterology)

  • Francesc J. Sancho

    (Hospital de la Santa Creu i Sant Pau, Department of Gastroenterology)

  • Mar Concepción

    (Hospital de la Santa Creu i Sant Pau, Department of Gastroenterology)

  • Teresa Ramón y Cajal

    (Hospital de la Santa Creu i Sant Pau, Department of Gastroenterology)

  • Justyna Szafranska

    (Hospital de la Santa Creu i Sant Pau, Department of Gastroenterology)

  • Michael O’Rorke

    (Queen’s University Belfast, Centre for Public Health, Belfast
    The University of Iowa, College of Public Health)

  • Liam Murray

    (Queen’s University Belfast, Centre for Public Health, Belfast)

  • Marie Cantwell

    (Queen’s University Belfast, Centre for Public Health, Belfast)

  • Victor M. Barberà

    (General University Hospital of Elche, Molecular Genetics Laboratory)

  • Javier Gallego

    (General University Hospital of Elche, Molecular Genetics Laboratory)

  • Adonina Tardón

    (Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Department of Medicine
    Instituto de Investigación Sanitaria del Principado de Asturias (ISPA)
    CIBERESP)

  • Luis Barneo

    (Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Department of Medicine)

  • MM Rodriguez-Suarez

    (Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Department of Medicine)

  • Enrique Domínguez-Muñoz

    (University Clinical Hospital of Santiago de Compostela, Department of Gastroenterology)

  • Yolanda Pazos

    (University Clinical Hospital of Santiago de Compostela, Department of Gastroenterology)

  • Antonio Lozano

    (University Clinical Hospital of Santiago de Compostela, Department of Gastroenterology)

  • Maria Luaces

    (University Clinical Hospital of Santiago de Compostela, Department of Gastroenterology)

  • Francisco Blanco-Antona

    (Salamanca; and CIBERONC, Department of Surgery, Hospital Universitario de Salamanca – IBSAL, Universidad de Salamanca)

  • J. M. Sayagués Manzano

    (Salamanca; and CIBERONC, Department of Surgery, Hospital Universitario de Salamanca – IBSAL, Universidad de Salamanca)

  • M. L. Gutiérrez Troncoso

    (Salamanca; and CIBERONC, Department of Surgery, Hospital Universitario de Salamanca – IBSAL, Universidad de Salamanca)

  • A. Orfao de Matos

    (Salamanca; and CIBERONC, Department of Surgery, Hospital Universitario de Salamanca – IBSAL, Universidad de Salamanca)

  • Luís Muñoz-Bellvís

    (Salamanca; and CIBERONC, Department of Surgery, Hospital Universitario de Salamanca – IBSAL, Universidad de Salamanca)

  • Thomas M. Gress

    (University Hospital of Giessen and Marburg, Department of Gastroenterology)

  • Malte Buchholz

    (University Hospital of Giessen and Marburg, Department of Gastroenterology)

  • Albrecht Neesse

    (University Hospital of Giessen and Marburg, Department of Gastroenterology)

  • William Greenhalf

    (University of Liverpool, Department of Molecular and Clinical Cancer Medicine)

  • Eithne Costello

    (University of Liverpool, Department of Molecular and Clinical Cancer Medicine)

  • Tatjana Crnogorac-Jurcevic

    (Queen Mary University of London, Barts Cancer Institute, Centre for Cancer Biomarkers and Biotherapeutics)

  • Hemant M. Kocher

    (Queen Mary University of London, Barts Cancer Institute, Centre for Cancer Biomarkers and Biotherapeutics)

  • Satyajit Bhattacharya

    (Queen Mary University of London, Barts Cancer Institute, Centre for Cancer Biomarkers and Biotherapeutics)

  • Ajit T. Abraham

    (Queen Mary University of London, Barts Cancer Institute, Centre for Cancer Biomarkers and Biotherapeutics)

  • Darren Ennis

    (Queen Mary University of London, Barts Cancer Institute, Centre for Cancer Biomarkers and Biotherapeutics)

  • Thomas Dowe

    (Queen Mary University of London, Barts Cancer Institute, Centre for Cancer Biomarkers and Biotherapeutics)

  • Tomasz Radon

    (Queen Mary University of London, Barts Cancer Institute, Centre for Cancer Biomarkers and Biotherapeutics)

  • Damian O’Driscoll

    (University College Cork, National Cancer Registry Ireland and HRB Clinical Research Facility)

  • Linda Sharp

    (University College Cork, National Cancer Registry Ireland and HRB Clinical Research Facility)

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.

Suggested Citation

  • Alberto Langtry & Raul Rabadan & Lola Alonso & Ioan Filip & Sergio Sabroso-Lasa & Ane Moreno-Oya & Rita Lawlor & Alfredo Carrato & Rafael Alvarez-Gallego & Mar Iglesias & Xavier Molero & Matthias J. L, 2025. "Deciphering the role of complement system genes in pancreatic cancer susceptibility and prognosis," Nature Communications, Nature, vol. 16(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-65811-y
    DOI: 10.1038/s41467-025-65811-y
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