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Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 11/2020

01-10-2020 | Gastric Cancer | Translational Research and Biomarkers

High RAD18 Expression is Associated with Disease Progression and Poor Prognosis in Patients with Gastric Cancer

Authors: Seded Baatar, MD, Tuya Bai, PhD, Takehiko Yokobori, MD, PhD, Navchaa Gombodorj, MD, PhD, Nobuhiro Nakazawa, MD, Yasunari Ubukata, MD, Akiharu Kimura, MD, PhD, Norimichi Kogure, MD, PhD, Akihiko Sano, MD, PhD, Makoto Sohda, MD, PhD, Makoto Sakai, MD, PhD, Amartuvshin Tumenjargal, MD, Kyoichi Ogata, MD, PhD, Hiroyuki Kuwano, MD, PhD, Ken Shirabe, MD, PhD, Hiroshi Saeki, MD, PhD

Published in: Annals of Surgical Oncology | Issue 11/2020

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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.
Appendix
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Metadata
Title
High RAD18 Expression is Associated with Disease Progression and Poor Prognosis in Patients with Gastric Cancer
Authors
Seded Baatar, MD
Tuya Bai, PhD
Takehiko Yokobori, MD, PhD
Navchaa Gombodorj, MD, PhD
Nobuhiro Nakazawa, MD
Yasunari Ubukata, MD
Akiharu Kimura, MD, PhD
Norimichi Kogure, MD, PhD
Akihiko Sano, MD, PhD
Makoto Sohda, MD, PhD
Makoto Sakai, MD, PhD
Amartuvshin Tumenjargal, MD
Kyoichi Ogata, MD, PhD
Hiroyuki Kuwano, MD, PhD
Ken Shirabe, MD, PhD
Hiroshi Saeki, MD, PhD
Publication date
01-10-2020
Publisher
Springer International Publishing
Published in
Annals of Surgical Oncology / Issue 11/2020
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-020-08518-2

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