RT Journal Article
T1 Deciphering CHFR Role in Pancreatic Ductal Adenocarcinoma
A1 Gonzalez-Borja, Iranzu
A1 Alors-Perez, Emilia
A1 Amat, Irene
A1 Alonso, Laura
A1 Viyuela-Garcia, Cristina
A1 Goni, Saioa
A1 Reyes, Jose C.
A1 Ceballos-Chavez, Maria
A1 Hernandez-Garcia, Irene
A1 Sanchez-Frias, Marina E.
A1 Santamaria, Enrique
A1 Razquin, Socorro
A1 Arjona-Sanchez, Alvaro
A1 Arrazubi, Virginia
A1 Perez-Sanz, Jairo
A1 Vera, Ruth
A1 Fernandez-Irigoyen, Joaquin
A1 Castano, Justo P.
A1 Viudez, Antonio
K1 pancreatic ductal adenocarcinoma (PDAC)
K1 DNA methylation
K1 checkpoint with forkhead and ring finger domains (CHFR)
K1 methylation
K1 immunohistochemistry (IHC)
K1 Gastric-cancer
K1 Promoter hypermethylation
K1 Methylation
K1 Checkpoint
K1 Aurora
K1 Inactivation
K1 Association
K1 Instability
K1 Carcinoma
K1 Ligase
AB 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.
PB Frontiers media sa
YR 2021
FD 2021-11-19
LK https://hdl.handle.net/10668/25875
UL https://hdl.handle.net/10668/25875
LA en
DS RISalud
RD Apr 12, 2025