Deciphering CHFR Role in Pancreatic Ductal Adenocarcinoma
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 a...
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| Language: | English |
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Frontiers Media S.A.
2021-11-01
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| Series: | Frontiers in Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmed.2021.720128/full |
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| author | Iranzu González-Borja Emilia Alors-Pérez Emilia Alors-Pérez Emilia Alors-Pérez Emilia Alors-Pérez Irene Amat Laura Alonso Cristina Viyuela-García Cristina Viyuela-García Cristina Viyuela-García Saioa Goñi José C. Reyes María Ceballos-Chávez Irene Hernández-García Marina E. Sánchez-Frías Marina E. Sánchez-Frías Marina E. Sánchez-Frías Enrique Santamaría Socorro Razquin Álvaro Arjona-Sánchez Álvaro Arjona-Sánchez Álvaro Arjona-Sánchez Virginia Arrazubi Jairo Pérez-Sanz Ruth Vera Joaquín Fernández-Irigoyen Justo P. Castaño Justo P. Castaño Justo P. Castaño Justo P. Castaño Antonio Viúdez Antonio Viúdez Antonio Viúdez |
| author_facet | Iranzu González-Borja Emilia Alors-Pérez Emilia Alors-Pérez Emilia Alors-Pérez Emilia Alors-Pérez Irene Amat Laura Alonso Cristina Viyuela-García Cristina Viyuela-García Cristina Viyuela-García Saioa Goñi José C. Reyes María Ceballos-Chávez Irene Hernández-García Marina E. Sánchez-Frías Marina E. Sánchez-Frías Marina E. Sánchez-Frías Enrique Santamaría Socorro Razquin Álvaro Arjona-Sánchez Álvaro Arjona-Sánchez Álvaro Arjona-Sánchez Virginia Arrazubi Jairo Pérez-Sanz Ruth Vera Joaquín Fernández-Irigoyen Justo P. Castaño Justo P. Castaño Justo P. Castaño Justo P. Castaño Antonio Viúdez Antonio Viúdez Antonio Viúdez |
| author_sort | Iranzu González-Borja |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-14T09:24:24Z |
| format | Article |
| id | doaj.art-aa8a20b687714e7c89f5590df6b0bb4f |
| institution | Directory Open Access Journal |
| issn | 2296-858X |
| language | English |
| last_indexed | 2024-12-14T09:24:24Z |
| publishDate | 2021-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Medicine |
| spelling | doaj.art-aa8a20b687714e7c89f5590df6b0bb4f2022-12-21T23:08:13ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2021-11-01810.3389/fmed.2021.720128720128Deciphering CHFR Role in Pancreatic Ductal AdenocarcinomaIranzu González-Borja0Emilia Alors-Pérez1Emilia Alors-Pérez2Emilia Alors-Pérez3Emilia Alors-Pérez4Irene Amat5Laura Alonso6Cristina Viyuela-García7Cristina Viyuela-García8Cristina Viyuela-García9Saioa Goñi10José C. Reyes11María Ceballos-Chávez12Irene Hernández-García13Marina E. Sánchez-Frías14Marina E. Sánchez-Frías15Marina E. Sánchez-Frías16Enrique Santamaría17Socorro Razquin18Álvaro Arjona-Sánchez19Álvaro Arjona-Sánchez20Álvaro Arjona-Sánchez21Virginia Arrazubi22Jairo Pérez-Sanz23Ruth Vera24Joaquín Fernández-Irigoyen25Justo P. Castaño26Justo P. Castaño27Justo P. Castaño28Justo P. Castaño29Antonio Viúdez30Antonio Viúdez31Antonio Viúdez32OncobionaTras Lab, Navarrabiomed, Complejo Hospitalario de Navarra, Universidad Pública de Navarra, Instituto de Investigación Sanitaria de Navarra, Pamplona, SpainHormones and Cancer Group, Maimonides Institute for Biomedical Research of Cordoba (IMIBIC), Córdoba, SpainDepartment of Cell Biology, Physiology, and Immunology, University of Córdoba, Córdoba, SpainReina Sofia University Hospital, Córdoba, SpainCentro de Investigación Biomédica en Red (CIBER) Fisiopatología de la Obesidad y Nutrición, Córdoba, SpainPathology Department, Complejo Hospitalario de Navarra, Pamplona, SpainPathology Department, Complejo Hospitalario de Navarra, Pamplona, SpainHormones and Cancer Group, Maimonides Institute for Biomedical Research of Cordoba (IMIBIC), Córdoba, SpainReina Sofia University Hospital, Córdoba, SpainSurgery Service, Reina Sofia University Hospital, Córdoba, SpainOncobionaTras Lab, Navarrabiomed, Complejo Hospitalario de Navarra, Universidad Pública de Navarra, Instituto de Investigación Sanitaria de Navarra, Pamplona, SpainCentro Andaluz de Biología Molecular y Medicina Regenerativa, Consejo Superior de Investigaciones Científicas-Universidad de Sevilla-Universidad Pablo de Olavide, Seville, SpainCentro Andaluz de Biología Molecular y Medicina Regenerativa, Consejo Superior de Investigaciones Científicas-Universidad de Sevilla-Universidad Pablo de Olavide, Seville, SpainMedical Oncology Department, Complejo Hospitalario de Navarra, Pamplona, SpainHormones and Cancer Group, Maimonides Institute for Biomedical Research of Cordoba (IMIBIC), Córdoba, SpainReina Sofia University Hospital, Córdoba, Spain0Pathology Service, Reina Sofia University Hospital, Córdoba, Spain1Proteomics Platform, Clinical Neuroproteomics Unit, Navarrabiomed, Complejo Hospitalario de Navarra, Universidad Pública de Navarra, Instituto de Investigación Sanitaria de Navarra, Pamplona, SpainPathology Department, Complejo Hospitalario de Navarra, Pamplona, SpainHormones and Cancer Group, Maimonides Institute for Biomedical Research of Cordoba (IMIBIC), Córdoba, SpainReina Sofia University Hospital, Córdoba, SpainSurgery Service, Reina Sofia University Hospital, Córdoba, SpainMedical Oncology Department, Complejo Hospitalario de Navarra, Pamplona, SpainOncobionaTras Lab, Navarrabiomed, Complejo Hospitalario de Navarra, Universidad Pública de Navarra, Instituto de Investigación Sanitaria de Navarra, Pamplona, SpainMedical Oncology Department, Complejo Hospitalario de Navarra, Pamplona, Spain1Proteomics Platform, Clinical Neuroproteomics Unit, Navarrabiomed, Complejo Hospitalario de Navarra, Universidad Pública de Navarra, Instituto de Investigación Sanitaria de Navarra, Pamplona, SpainHormones and Cancer Group, Maimonides Institute for Biomedical Research of Cordoba (IMIBIC), Córdoba, SpainDepartment of Cell Biology, Physiology, and Immunology, University of Córdoba, Córdoba, SpainReina Sofia University Hospital, Córdoba, SpainCentro de Investigación Biomédica en Red (CIBER) Fisiopatología de la Obesidad y Nutrición, Córdoba, SpainOncobionaTras Lab, Navarrabiomed, Complejo Hospitalario de Navarra, Universidad Pública de Navarra, Instituto de Investigación Sanitaria de Navarra, Pamplona, SpainMedical Oncology Department, Complejo Hospitalario de Navarra, Pamplona, Spain2Medical Affairs Services, ICON plc, North Wales, PA, United StatesCheckpoint 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.https://www.frontiersin.org/articles/10.3389/fmed.2021.720128/fullpancreatic ductal adenocarcinoma (PDAC)DNA methylationcheckpoint with forkhead and ring finger domains (CHFR)methylationimmunohistochemistry (IHC) |
| spellingShingle | Iranzu González-Borja Emilia Alors-Pérez Emilia Alors-Pérez Emilia Alors-Pérez Emilia Alors-Pérez Irene Amat Laura Alonso Cristina Viyuela-García Cristina Viyuela-García Cristina Viyuela-García Saioa Goñi José C. Reyes María Ceballos-Chávez Irene Hernández-García Marina E. Sánchez-Frías Marina E. Sánchez-Frías Marina E. Sánchez-Frías Enrique Santamaría Socorro Razquin Álvaro Arjona-Sánchez Álvaro Arjona-Sánchez Álvaro Arjona-Sánchez Virginia Arrazubi Jairo Pérez-Sanz Ruth Vera Joaquín Fernández-Irigoyen Justo P. Castaño Justo P. Castaño Justo P. Castaño Justo P. Castaño Antonio Viúdez Antonio Viúdez Antonio Viúdez Deciphering CHFR Role in Pancreatic Ductal Adenocarcinoma Frontiers in Medicine pancreatic ductal adenocarcinoma (PDAC) DNA methylation checkpoint with forkhead and ring finger domains (CHFR) methylation immunohistochemistry (IHC) |
| title | Deciphering CHFR Role in Pancreatic Ductal Adenocarcinoma |
| title_full | Deciphering CHFR Role in Pancreatic Ductal Adenocarcinoma |
| title_fullStr | Deciphering CHFR Role in Pancreatic Ductal Adenocarcinoma |
| title_full_unstemmed | Deciphering CHFR Role in Pancreatic Ductal Adenocarcinoma |
| title_short | Deciphering CHFR Role in Pancreatic Ductal Adenocarcinoma |
| title_sort | deciphering chfr role in pancreatic ductal adenocarcinoma |
| topic | pancreatic ductal adenocarcinoma (PDAC) DNA methylation checkpoint with forkhead and ring finger domains (CHFR) methylation immunohistochemistry (IHC) |
| url | https://www.frontiersin.org/articles/10.3389/fmed.2021.720128/full |
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