AUTHOR=González-Borja Iranzu , Alors-Pérez Emilia , Amat Irene , Alonso Laura , Viyuela-García Cristina , Goñi Saioa , Reyes José C. , Ceballos-Chávez María , Hernández-García Irene , Sánchez-Frías Marina E. , Santamaría Enrique , Razquin Socorro , Arjona-Sánchez Álvaro , Arrazubi Virginia , Pérez-Sanz Jairo , Vera Ruth , Fernández-Irigoyen Joaquín , Castaño Justo P. , Viúdez Antonio 

TITLE=Deciphering CHFR Role in Pancreatic Ductal Adenocarcinoma

JOURNAL=Frontiers in Medicine

VOLUME=8

YEAR=2021

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2021.720128

DOI=10.3389/fmed.2021.720128

ISSN=2296-858X

ABSTRACT=<p>Checkpoint with forkhead-associated and ring finger domains (<italic>CHFR</italic>) 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 <italic>CHFR</italic> in PDAC and evaluating <italic>CHFR</italic> 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 (<italic>n</italic> = 19) or resectable (<italic>n</italic> = 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 <italic>CHFR</italic> 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.</p>