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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Frontiers Media S.A.
2021
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oai:doaj.org-article:aa8a20b687714e7c89f5590df6b0bb4f2021-11-19T05:08:31ZDeciphering CHFR Role in Pancreatic Ductal Adenocarcinoma2296-858X10.3389/fmed.2021.720128https://doaj.org/article/aa8a20b687714e7c89f5590df6b0bb4f2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fmed.2021.720128/fullhttps://doaj.org/toc/2296-858XCheckpoint 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.Iranzu González-BorjaEmilia Alors-PérezEmilia Alors-PérezEmilia Alors-PérezEmilia Alors-PérezIrene AmatLaura AlonsoCristina Viyuela-GarcíaCristina Viyuela-GarcíaCristina Viyuela-GarcíaSaioa GoñiJosé C. ReyesMaría Ceballos-ChávezIrene Hernández-GarcíaMarina E. Sánchez-FríasMarina E. Sánchez-FríasMarina E. Sánchez-FríasEnrique SantamaríaSocorro RazquinÁlvaro Arjona-SánchezÁlvaro Arjona-SánchezÁlvaro Arjona-SánchezVirginia ArrazubiJairo Pérez-SanzRuth VeraJoaquín Fernández-IrigoyenJusto P. CastañoJusto P. CastañoJusto P. CastañoJusto P. CastañoAntonio ViúdezAntonio ViúdezAntonio ViúdezFrontiers Media S.A.articlepancreatic ductal adenocarcinoma (PDAC)DNA methylationcheckpoint with forkhead and ring finger domains (CHFR)methylationimmunohistochemistry (IHC)Medicine (General)R5-920ENFrontiers in Medicine, Vol 8 (2021) |
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| collection |
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EN |
| topic |
pancreatic ductal adenocarcinoma (PDAC) DNA methylation checkpoint with forkhead and ring finger domains (CHFR) methylation immunohistochemistry (IHC) Medicine (General) R5-920 |
| spellingShingle |
pancreatic ductal adenocarcinoma (PDAC) DNA methylation checkpoint with forkhead and ring finger domains (CHFR) methylation immunohistochemistry (IHC) Medicine (General) R5-920 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 |
| 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. |
| format |
article |
| 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 |
| title |
Deciphering CHFR Role in Pancreatic Ductal Adenocarcinoma |
| title_short |
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_sort |
deciphering chfr role in pancreatic ductal adenocarcinoma |
| publisher |
Frontiers Media S.A. |
| publishDate |
2021 |
| url |
https://doaj.org/article/aa8a20b687714e7c89f5590df6b0bb4f |
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