4.7 Article

A Novel DNA Replication-Related Signature Predicting Recurrence After R0 Resection of Pancreatic Ductal Adenocarcinoma: Prognostic Value and Clinical Implications

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出版社

FRONTIERS MEDIA SA
DOI: 10.3389/fcell.2021.619549

关键词

DNA replication; pancreatic ductal adenocarcinoma; prognostic signature; risk score; R0 resection; recurrence

资金

  1. National Natural Science Foundation of China [81672325, 81802316]

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The study aims to develop a DNA replication-related gene signature to stratify PDAC patients treated with R0 resection based on recurrence risks. Pathway enrichment analysis suggests a close relationship with cell cycle, DNA replication, and DNA repair, potentially aiding in the identification of novel biomarkers and therapeutic targets for PDAC.
The aim of any surgical resection for pancreatic ductal adenocarcinoma (PDAC) is to achieve tumor-free margins (R0). R0 margins give rise to better outcomes than do positive margins (R1). Nevertheless, postoperative morbidity after R0 resection remains high and prognostic gene signature predicting recurrence risk of patients in this subgroup is blank. Our study aimed to develop a DNA replication-related gene signature to stratify the R0-treated PDAC patients with various recurrence risks. We conducted Cox regression analysis and the LASSO algorithm on 273 DNA replication-related genes and eventually constructed a 7-gene signature. The predictive capability and clinical feasibility of this risk model were assessed in both training and external validation sets. Pathway enrichment analysis showed that the signature was closely related to cell cycle, DNA replication, and DNA repair. These findings may shed light on the identification of novel biomarkers and therapeutic targets for PDAC.

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