Publication:
Deciphering CHFR role in pancreatic ductal adenocarcinoma

Date

2021

Authors

González Borja, Iranzu
Alors-Pérez, Emilia
Alonso, Laura
Viyuela-García, Cristina
Reyes, José C.
Ceballos-Chávez, María
Hernández García, Irene
Sánchez-Frías, Marina E.

Director

Publisher

Frontiers Media
Acceso abierto / Sarbide irekia
Artículo / Artikulua
Versión publicada / Argitaratu den bertsioa

Project identifier

MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/BFU2016-80360-R
AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-105201RB-I00/ES/recolecta

Abstract

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.

Description

Keywords

Checkpoint with forkhead and ring finger domains (CHFR), DNA methylation, Immunohistochemistry (IHC), Methylation, Pancreatic ductal adenocarcinoma (PDAC)

Department

Ciencias de la Salud / Osasun Zientziak

Faculty/School

Degree

Doctorate program

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Creative Commons Attribution 4.0 International

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