High RAD18 Expression is Associated with Disease Progression and Poor Prognosis in Patients with Gastric Cancer.
Journal
Annals of surgical oncology
ISSN: 1534-4681
Titre abrégé: Ann Surg Oncol
Pays: United States
ID NLM: 9420840
Informations de publication
Date de publication:
Oct 2020
Oct 2020
Historique:
received:
02
09
2019
pubmed:
2
5
2020
medline:
2
4
2021
entrez:
2
5
2020
Statut:
ppublish
Résumé
RAD18 plays an important role in DNA damage repair by inducing monoubiquitinated PCNA (mUB-PCNA) in both cancer and normal tissues. Previous studies have not determined the significance of RAD18 expression in clinical gastric cancer (GC) samples. Thus, this study aimed to clarify the expression and functional significance of RAD18 in GC. Overall, 96 resected GC samples were subjected to an immunohistochemical analysis of RAD18. GC cell lines were also subjected to functional RNA interference analyses of RAD18. RAD18 expression was predominantly nuclear and was observed at higher levels in GC tissues than in normal tissues. In GC tissues, strong RAD18 expression was associated with progression of lymph node metastasis (p = 0.0001), lymphatic invasion (p = 0.0255), venous invasion (p < 0.0001), recurrence (p = 0.028), and disease stage (p = 0.0253). Moreover, GC patients with high tumor RAD18 expression had shorter overall survival (p = 0.0061) and recurrence-free survival durations (p = 0.035) than those with low tumor RAD18 expression. RAD18 knockdown inhibited GC proliferation and invasiveness and increased chemosensitivity by suppressing mUB-PCNA. RAD18 expression may be a useful marker of progression and poor prognosis of GC. Moreover, therapeutic strategies that target RAD18 might be a novel chemosensitizer to eradicate the refractory GC.
Sections du résumé
BACKGROUND
BACKGROUND
RAD18 plays an important role in DNA damage repair by inducing monoubiquitinated PCNA (mUB-PCNA) in both cancer and normal tissues. Previous studies have not determined the significance of RAD18 expression in clinical gastric cancer (GC) samples. Thus, this study aimed to clarify the expression and functional significance of RAD18 in GC.
METHODS
METHODS
Overall, 96 resected GC samples were subjected to an immunohistochemical analysis of RAD18. GC cell lines were also subjected to functional RNA interference analyses of RAD18.
RESULTS
RESULTS
RAD18 expression was predominantly nuclear and was observed at higher levels in GC tissues than in normal tissues. In GC tissues, strong RAD18 expression was associated with progression of lymph node metastasis (p = 0.0001), lymphatic invasion (p = 0.0255), venous invasion (p < 0.0001), recurrence (p = 0.028), and disease stage (p = 0.0253). Moreover, GC patients with high tumor RAD18 expression had shorter overall survival (p = 0.0061) and recurrence-free survival durations (p = 0.035) than those with low tumor RAD18 expression. RAD18 knockdown inhibited GC proliferation and invasiveness and increased chemosensitivity by suppressing mUB-PCNA.
CONCLUSIONS
CONCLUSIONS
RAD18 expression may be a useful marker of progression and poor prognosis of GC. Moreover, therapeutic strategies that target RAD18 might be a novel chemosensitizer to eradicate the refractory GC.
Identifiants
pubmed: 32356270
doi: 10.1245/s10434-020-08518-2
pii: 10.1245/s10434-020-08518-2
doi:
Substances chimiques
Biomarkers, Tumor
0
DNA-Binding Proteins
0
RAD18 protein, human
0
Ubiquitin-Protein Ligases
EC 2.3.2.27
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
4360-4368Subventions
Organisme : Japan Society for the Promotion of Science (JSPS)
ID : 17K19893
Organisme : Japan Society for the Promotion of Science (JSPS)
ID : 18H02877
Organisme : Japan Society for the Promotion of Science (JSPS)
ID : 18K07665
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