High RAD18 Expression is Associated with Disease Progression and Poor Prognosis in Patients with Gastric Cancer
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ORIGINAL ARTICLE – TRANSLATIONAL RESEARCH AND BIOMARKERS
High RAD18 Expression is Associated with Disease Progression and Poor Prognosis in Patients with Gastric Cancer Seded Baatar, MD1, Tuya Bai, PhD1, Takehiko Yokobori, MD, PhD1,2, Navchaa Gombodorj, MD, PhD2,3, Nobuhiro Nakazawa, MD1, Yasunari Ubukata, MD1, Akiharu Kimura, MD, PhD1, Norimichi Kogure, MD, PhD1, Akihiko Sano, MD, PhD1, Makoto Sohda, MD, PhD1, Makoto Sakai, MD, PhD1, Amartuvshin Tumenjargal, MD4, Kyoichi Ogata, MD, PhD1, Hiroyuki Kuwano, MD, PhD1, Ken Shirabe, MD, PhD1, and Hiroshi Saeki, MD, PhD1 1
Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi, Japan; 2Research Program for Omics-Based Medical Science, Division of Integrated Oncology Research, Gunma University Initiative for Advanced Research (GIAR), Maebashi, Japan; 3Department of Radiation Oncology, National Cancer Center of Mongolia, Ulaanbaatar, Mongolia; 4Department of Bioimaging and Information Analysis, Graduate School of Medicine, Gunma University, Maebashi, Japan
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
Electronic supplementary material The online version of this article (https://doi.org/10.1245/s10434-020-08518-2) contains supplementary material, which is available to authorized users. Ó Society of Surgical Oncology 2020 First Received: 2 September 2019 T. Yokobori, MD, PhD e-mail: [email protected]
(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.
Gastric cancer (GC) is the fifth most common cancer and a leading cause of cancer-related deaths worldwide.1 Patients with operable GC should undergo surgical resection as a curative treatment. Postoperative chemotherapy can improve patient survival and prevent disease recurrence.2 Acc
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