ASO Author Reflections: High RAD18 Expression is Associated with Disease Progression and Poor Prognosis for Patients wit
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ASO AUTHOR REFLECTIONS
ASO Author Reflections: High RAD18 Expression is Associated with Disease Progression and Poor Prognosis for Patients with Gastric Cancer Takehiko Yokobori, MD, PhD1,2, Navchaa Gombodorj, MD, PhD2,3, Kyoichi Ogata, MD, PhD1, Makoto Sohda, 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, Gunma, Japan; Research Program for Omics-Based Medical Science, Division of Integrated Oncology Research, Gunma University Initiative for Advanced Research (GIAR), Maebashi, Gunma, Japan; 3Department of Radiation Oncology, National Cancer Center of Mongolia, Ulaanbaatar, Mongolia 2
Useful biomarkers and therapeutic targets are needed to improve prognoses for refractory gastric cancer (GC) patients. The RAD18 gene, a DNA repair protein, plays a critical role in initiating DNA damage repair-signaling and acts as an E3 ligase to mono-ubiquitinate proliferating cell nuclear antigen (PCNA) to yield mono-ubiquitinated PCNA (mUB-PCNA), an essential regulator of DNA repair.1–4 In this study, suppression of RAD18 was associated with DNA damage accumulation induced by ultraviolet (UV) irradiation and the anticancer drug CDDP mediated by mUB-PCNA inhibition.2 However, the expression significance and function of RAD18 has not been elucidated in GC to date. Nuclear RAD18 expression in GC was higher than in normal tissues. High RAD18 expression in GC was associated with cancer progression and recurrence. Gastric cancer patients with high RAD18 had poorer overall and recurrence-free survival rates than those with low expression.5 On the other hand, this study could not show the chemosensitivity predictive value of pre-treatment RAD18 expression in advanced GC samples treated by chemotherapy. The in vitro analyses clarified that RAD18
knockdown in GC cell lines inhibited proliferation and invasiveness and enhanced chemo-sensitivity via suppression of mUB-PCNA.5 Future study is expected to clarify the significance of RAD18 as a chemosensitivity predictor using GC samples before and after chemotherapy. Moreover, further studies are needed to develop the RAD18 targeted agent for refractory GC patients. The combination of chemotherapy and RAD18-targeted therapy may be a promising strategy against chemoresistant GC. Another approach to searching for therapeutic strategy against chemoresistant GC involves focusing on other RAD family proteins as particular targeted agents. The authors recently reported that positive RAD51 (a key molecule that controls the DNA double-strand break repair pathway) expression was identified as a useful biomarker for predicting resistance to preoperative therapy for esophageal cancer.6 Both well-designed clinical and basic studies for chemoresistant GC are urgently required. COMPLIANCE WITH ETHICAL STANDARDS DISCLOSURE interest.
All authors declare that they have no conflict of
REFERENCES Ó Society of Surgical Oncology 2020 First Received: 20 April 2020 T. Yokobo
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