RRC ID 63697
Author Baatar S, Bai T, Yokobori T, Gombodorj N, Nakazawa N, Ubukata Y, Kimura A, Kogure N, Sano A, Sohda M, Sakai M, Tumenjargal A, Ogata K, Kuwano H, Shirabe K, Saeki H.
Title High RAD18 Expression is Associated with Disease Progression and Poor Prognosis in Patients with Gastric Cancer.
Journal Ann Surg Oncol
Abstract 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: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: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: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.
Volume 27(11)
Pages 4360-4368
Published 2020-10-1
DOI 10.1245/s10434-020-08518-2
PII 10.1245/s10434-020-08518-2
PMID 32356270
MeSH Biomarkers, Tumor / biosynthesis Biomarkers, Tumor / genetics Cell Line, Tumor DNA-Binding Proteins* / biosynthesis DNA-Binding Proteins* / genetics Disease Progression Humans Neoplasm Invasiveness Prognosis Stomach Neoplasms* / genetics Stomach Neoplasms* / metabolism Stomach Neoplasms* / pathology Ubiquitin-Protein Ligases* / biosynthesis Ubiquitin-Protein Ligases* / genetics
IF 4.061
Human and Animal Cells MKN7(RCB0999) MKN74(RCB1002) MKN45(RCB1001) GCIY(RCB0555)