1. Deciphering CHFR Role in Pancreatic Ductal Adenocarcinoma
- Author
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Iranzu González-Borja, Emilia Alors-Pérez, Irene Amat, Laura Alonso, Cristina Viyuela-García, Saioa Goñi, José C. Reyes, María Ceballos-Chávez, Irene Hernández-García, Marina E. Sánchez-Frías, Enrique Santamaría, Socorro Razquin, Álvaro Arjona-Sánchez, Virginia Arrazubi, Jairo Pérez-Sanz, Ruth Vera, Joaquín Fernández-Irigoyen, Justo P. Castaño, Antonio Viúdez, Diputación Foral de Navarra, Sociedad Española de Oncología Médica, Fundación 'la Caixa', Fundación Caja Navarra, Ministerio de Economía y Competitividad (España), Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Instituto de Salud Carlos III, European Commission, Junta de Andalucía, Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición (España), Universidad Pública de Navarra. Departamento de Ciencias de la Salud, Nafarroako Unibertsitate Publikoa. Osasun Zientziak Saila, Gobierno de Navarra / Nafarroako Gobernua, [González-Borja,I, Goñi,S, Pérez-Sanz,J, Viúdez,A] OncobionaTras Lab, Navarrabiomed, Complejo Hospitalario de Navarra, Universidad Pública de Navarra, Instituto de Investigación Sanitaria de Navarra, Pamplona, Spain. [Alors-Pérez,E, Viyuela-García,C, Sánchez-Frías,ME, Arjona-Sánchez,Á, Castaño,JP] Hormones and Cancer Group, Maimonides Institute for Biomedical Research of Cordoba (IMIBIC), Córdoba, Spain. [Alors-Pérez,E, Castaño,JP] Department of Cell Biology, Physiology, and Immunology, University of Córdoba, Córdoba, Spain. [Alors-Pérez,E, Castaño,JP] Reina Sofia University Hospital, Córdoba, Spain. [Alors-Pérez,E, Castaño,JP] Centro de Investigación Biomédica en Red (CIBER) Fisiopatología de la Obesidad y Nutrición, Córdoba, Spain. [Amat,I, Alonso,L, Razquin,S] Pathology Department, Complejo Hospitalario de Navarra, Pamplona, Spain. [Viyuela-García,C, Arjona-Sánchez,Á] Surgery Service, Reina Sofia University Hospital, Córdoba, Spain. [Reyes,JC, Ceballos-Chávez,M] Centro Andaluz de Biología Molecular y Medicina Regenerativa, Consejo Superior de Investigaciones Científicas-Universidad de Sevilla-Universidad Pablo de Olavide, Seville, Spain. [Hernández-García,I, Arrazubi,V, Vera,R, Viúdez,A] Medical Oncology Department, Complejo Hospitalario de Navarra, Pamplona, Spain. [Sánchez-Frías,ME] Pathology Service, Reina Sofia University Hospital, Córdoba, Spain. [Santamaría,E, Fernández-Irigoyen,J] Proteomics Platform, Clinical Neuroproteomics Unit, Navarrabiomed, Complejo Hospitalario de Navarra, Universidad Pública de Navarra, Instituto de Investigación Sanitaria de Navarra, Pamplona, Spain. [Viúdez,A] Medical Affairs Services, ICON plc, North Wales, PA, United States., This work was funded by grants from the Department of Health from the Government of Navarra (Ref. 008-2018), REFBIO II Pyrenees Biomedical Network from Programa INTERREG V-A España-Francia-Andorra (Ref. BMK_PANC) and Sociedad Española de Oncología Médica (SEOM) to AV. IG-B was supported by a predoctoral fellowship from the Department of Economic Development Government of Navarre Ayudas para la contratación de doctorandos y doctorandas por empresas y organismos de investigación y difusión de conocimientos: doctorados industriales 2018–2020. Intensification Programme Navarrabiomed 2017-2021 Obra Social La Caixa Fundación Caja Navarra. This work has also been supported by the Spanish Ministry of Economy [MINECO, BFU2016-80360-R (to JC)] and the Ministry of Science and Innovation [MICINN, PID2019- 105201RB-I00 (to JC)]. Instituto de Salud Carlos III, co-funded by European Union (ERDF/ESF, Investing in your future) [Predoctoral contract FI17/00282 (to EA-P)]. Junta de Andalucía (BIO-0139), GETNE2016 and GETNE2019 Research grants (to JC), and and CIBERobn.
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Medicine (General) ,Pancreatic ductal adenocarcinoma ,Pancreatic ductal adenocarcinoma (PDAC) ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Sequence Analysis::High-Throughput Nucleotide Sequencing [Medical Subject Headings] ,Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Molecular Structure::Molecular Conformation::Protein Conformation::Protein Structure, Tertiary::Protein Interaction Domains and Motifs::RING Finger Domains [Medical Subject Headings] ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Combined Modality Therapy::Neoadjuvant Therapy [Medical Subject Headings] ,Methylation ,Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings] ,Chemicals and Drugs::Organic Chemicals::Hydrocarbons::Hydrocarbons, Cyclic::Hydrocarbons, Alicyclic::Cycloparaffins::Cyclodecanes::Taxoids [Medical Subject Headings] ,R5-920 ,CHFR ,Diseases::Neoplasms::Neoplasms by Histologic Type::Neoplasms, Glandular and Epithelial::Carcinoma::Adenocarcinoma [Medical Subject Headings] ,Medicine ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Prognosis::Disease-Free Survival [Medical Subject Headings] ,Checkpoint with forkhead and ring finger domains (CHFR) ,DNA methylation ,business.industry ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Nucleic Acid Amplification Techniques::Polymerase Chain Reaction [Medical Subject Headings] ,General Medicine ,Brief Research Report ,Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids::RNA::RNA, Messenger [Medical Subject Headings] ,Immunohistochemistry (IHC) ,Metilación ,Cancer research ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Prognosis [Medical Subject Headings] ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Clinical Laboratory Techniques::Cytological Techniques::Histocytochemistry::Immunohistochemistry [Medical Subject Headings] ,business ,Carcinoma ductal pancreático ,Chemicals and Drugs::Biological Factors::Biological Markers::Biomarkers, Pharmacological [Medical Subject Headings] ,Metilación de ADN ,Inmunohistoquímica ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Clinical Laboratory Techniques::Cytological Techniques::Histocytological Preparation Techniques::Staining and Labeling [Medical Subject Headings] - Abstract
Checkpoint with forkhead-associated and ring finger domains (CHFR) has been proposed as a predictive and prognosis biomarker for different tumor types, but its role in pancreatic ductal adenocarcinoma (PDAC) remains unknown. The aim of this study was two-pronged: to review the role of CHFR in PDAC and evaluating CHFR as a potential predictive biomarker in this disease. For this purpose, we first explored the CHFR messenger (m)RNA expression and promoter methylation through the TCGA database. Secondly, the CHFR expression and promoter methylation were prospectively evaluated in a cohort of patients diagnosed with borderline (n = 19) or resectable (n = 16) PDAC by immunohistochemistry (IHC), methylation specific-PCR (MSP), and pyrosequencing. The results from the TCGA database showed significant differences in terms of progression-free survival (PFS) and overall survival (OS) based on the CHFR mRNA expression, which was likely independent from the promoter methylation. Importantly, our results showed that in primarily resected patients and also the entire cohort, a higher CHFR expression as indicated by the higher IHC staining intensity might identify patients with longer disease-free survival (DFS) and OS, respectively. Similarly, in the same cohorts, patients with lower methylation levels by pyrosequencing showed significantly longer OS than patients without this pattern. Both, the CHFR expression intensity and its promoter methylation were established as independent prognostic factors for PFS and OS in the entire cohort. In contrast, no significant differences were found between different methylation patterns for CHFR and the response to taxane-based neoadjuvant treatment. These results suggest the potential role of the higher expression of CHFR and the methylation pattern of its promoter as potential prognostic biomarkers in PDAC, thus warranting further comprehensive studies to extend and confirm our preliminary findings., This work was funded by grants from the Department of Health from the Government of Navarra (Ref. 008-2018), REFBIO II Pyrenees Biomedical Network from Programa INTERREG V-A España-Francia-Andorra (Ref. BMK_PANC) and Sociedad Española de Oncología Médica (SEOM) to AV. IG-B was supported by a predoctoral fellowship from the Department of Economic Development Government of Navarre Ayudas para la contratación de doctorandos y doctorandas por empresas y organismos de investigación y difusión de conocimientos: doctorados industriales 2018–2020. Intensification Programme Navarrabiomed 2017-2021 Obra Social La Caixa Fundación Caja Navarra. This work has also been supported by the Spanish Ministry of Economy [MINECO; BFU2016-80360-R (to JC)] and the Ministry of Science and Innovation [MICINN; PID2019- 105201RB-I00 (to JC)]. Instituto de Salud Carlos III, co-funded by European Union (ERDF/ESF, Investing in your future) [Predoctoral contract FI17/00282 (to EA-P)]. Junta de Andalucía (BIO-0139); GETNE2016 and GETNE2019 Research grants (to JC); and CIBERobn.
- Published
- 2021
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