Back to Search
Start Over
REV7 is involved in outcomes of platinum-based chemotherapy in pancreatic cancer by controlling the DNA damage response.
- Source :
-
Cancer science [Cancer Sci] 2024 Feb; Vol. 115 (2), pp. 660-671. Date of Electronic Publication: 2023 Dec 21. - Publication Year :
- 2024
-
Abstract
- REV7 is a multifunctional protein implicated in various biological processes, including DNA damage response. REV7 expression in human cancer cells affects their sensitivity to DNA-damaging agents. In the present study, we investigated the significance of REV7 in pancreatic ductal adenocarcinoma (PDAC). REV7 expression was immunohistochemically examined in 92 resected PDAC specimens and 60 endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNAB) specimens of unresectable PDAC treated with platinum-based chemotherapy, and its association with clinicopathologic features was analyzed. Although REV7 expression was not significantly associated with the progression of primary tumors (T-factor and Stage) in either resected or unresectable PDAC, decreased levels of REV7 expression in EUS-FNAB specimens of unresectable PDAC were significantly associated with better outcomes of platinum-based chemotherapy and a favorable prognosis. REV7-deficient PDAC cell lines showed suppressed cell growth and enhanced sensitivity to cisplatin in vitro. Tumor-bearing mice generated using REV7-deficient PDAC cell lines also showed enhanced sensitivity to cisplatin in vivo. RNA sequencing analysis using WT and REV7-deficient PDAC cell lines revealed that REV7 inactivation promoted the downregulation of genes involved in the DNA repair and the upregulation of genes involved in apoptosis. Our results indicate that decreased expression of REV7 is associated with better outcomes of platinum-based chemotherapy in PDAC by suppressing the DNA damage response. It is also suggested that REV7 is a useful biomarker for predicting the outcome of platinum-based chemotherapy and the prognosis of unresectable PDAC and is a potential target for PDAC treatment.<br /> (© 2023 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)
- Subjects :
- Humans
Animals
Mice
Cisplatin pharmacology
Cisplatin therapeutic use
Platinum therapeutic use
DNA Repair genetics
Pancreatic Neoplasms drug therapy
Pancreatic Neoplasms genetics
Pancreatic Neoplasms metabolism
Carcinoma, Pancreatic Ductal drug therapy
Carcinoma, Pancreatic Ductal genetics
Carcinoma, Pancreatic Ductal metabolism
Adenocarcinoma drug therapy
Biological Phenomena
Subjects
Details
- Language :
- English
- ISSN :
- 1349-7006
- Volume :
- 115
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Cancer science
- Publication Type :
- Academic Journal
- Accession number :
- 38130032
- Full Text :
- https://doi.org/10.1111/cas.16044