González-Borja, IranzuAlors-Pérez, EmiliaAmat, IreneAlonso, LauraViyuela-García, CristinaGoñi, SaioaReyes, José C.Ceballos-Chávez, MaríaHernández-García, IreneSánchez-Frías, Marina E.Santamaría, EnriqueRazquin, SocorroArjona-Sánchez, ÁlvaroArrazubi, VirginiaPérez-Sanz, JairoVera, RuthFernández-Irigoyen, JoaquínCastaño, Justo P.Viúdez, Antonio2022-09-052022-09-052021-11-19González-Borja I, Alors-Pérez E, Amat I, Alonso L, Viyuela-García C, Goñi S, et al. Deciphering CHFR Role in Pancreatic Ductal Adenocarcinoma. Front Med. 2021 Nov 19;8:720128http://hdl.handle.net/10668/3996Checkpoint 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.enAtribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/Pancreatic ductal adenocarcinoma (PDAC)DNA methylationCheckpoint with forkhead and ring finger domains (CHFR)MethylationImmunohistochemistry (IHC)Carcinoma ductal pancreáticoMetilación de ADNMetilaciónInmunohistoquímicaMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::PrognosisMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Prognosis::Disease-Free SurvivalMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Clinical Laboratory Techniques::Cytological Techniques::Histocytochemistry::ImmunohistochemistryMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Combined Modality Therapy::Neoadjuvant TherapyMedical 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 DomainsMedical Subject Headings::Diseases::Neoplasms::Neoplasms by Histologic Type::Neoplasms, Glandular and Epithelial::Carcinoma::AdenocarcinomaMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Nucleic Acid Amplification Techniques::Polymerase Chain ReactionMedical Subject Headings::Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids::RNA::RNA, MessengerMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Sequence Analysis::High-Throughput Nucleotide SequencingMedical Subject Headings::Chemicals and Drugs::Biological Factors::Biological Markers::Biomarkers, PharmacologicalMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Clinical Laboratory Techniques::Cytological Techniques::Histocytological Preparation Techniques::Staining and LabelingMedical Subject Headings::Chemicals and Drugs::Organic Chemicals::Hydrocarbons::Hydrocarbons, Cyclic::Hydrocarbons, Alicyclic::Cycloparaffins::Cyclodecanes::TaxoidsDeciphering CHFR Role in Pancreatic Ductal Adenocarcinomaresearch article34869418open access10.3389/fmed.2021.7201282296-858XPMC8639583