Enhanced AZIN1 RNA editing and overexpression of its regulatory enzyme ADAR1 are important prognostic biomarkers in gastric cancer

Yoshinaga Okugawa, Yuji Toiyama, Kunitoshi Shigeyasu, Akira Yamamoto, Tsunehiko Shigemori, Chengzeng Yin, Takashi Ichikawa, Hiromi Yasuda, Hiroyuki Fujikawa, Shigeyuki Yoshiyama, Junichiro Hiro, Masaki Ohi, Toshimitsu Araki, Masato Kusunoki, Ajay Goel

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Background: Adenosine-to-inosine (A-to-I) RNA editing is catalyzed by adenosine deaminases acting on RNA (ADAR) enzymes. Recent evidence suggests that RNA editing of antizyme inhibitor 1 (AZIN1) RNA is emerging as a key epigenetic alteration underlying cancer pathogenesis. Methods: We evaluated AZIN1 RNA editing levels, and the expression of its regulator, ADAR1, in 280 gastric tissues from 140 patients, using a RNA editing site-specific quantitative polymerase chain reaction assays. We also analyzed the clinical significance of these results as disease biomarkers in gastric cancer (GC) patients. Results: Both AZIN1 RNA editing levels and ADAR1 expression were significantly elevated in GC tissues compared with matched normal mucosa (P < 0.0001, 0.0008, respectively); and AZIN1 RNA editing was positively correlated with ADAR1 expression. Elevated expression of ADAR1 significantly correlated with poor overall survival (P = 0.034), while hyper-edited AZIN1 emerged as an independent prognostic factor for OS and disease-free survival in GC patients [odds ratio (OR):1.98, 95% CI 1.17-3.35, P = 0.011, OR: 4.55, 95% CI 2.12-9.78, P = 0.0001, respectively]. Increased AZIN1 RNA editing and ADAR1 over-expression were significantly correlated with key clinicopathological factors, such as advanced T stage, presence of lymph node metastasis, distant metastasis, and higher TNM stages in GC patients. Logistic regression analysis revealed that hyper-editing status of AZIN1 RNA was an independent risk factor for lymph node metastasis in GC patients [hazard ratio (HR):3.03, 95% CI 1.19-7.71, P = 0.02]. Conclusions: AZIN1 RNA editing levels may be an important prognostic biomarker in GC patients, and may serve as a key clinical decision-making tool for determining preoperative treatment strategies in GC patients.

Original languageEnglish
Article number366
JournalJournal of Translational Medicine
Volume16
Issue number1
DOIs
Publication statusPublished - Dec 18 2018

Keywords

  • AZIN1
  • Gastric cancer
  • Lymph node metastasis
  • Peritoneal metastasis
  • Prognosis
  • RNA editing

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Fingerprint Dive into the research topics of 'Enhanced AZIN1 RNA editing and overexpression of its regulatory enzyme ADAR1 are important prognostic biomarkers in gastric cancer'. Together they form a unique fingerprint.

  • Cite this

    Okugawa, Y., Toiyama, Y., Shigeyasu, K., Yamamoto, A., Shigemori, T., Yin, C., Ichikawa, T., Yasuda, H., Fujikawa, H., Yoshiyama, S., Hiro, J., Ohi, M., Araki, T., Kusunoki, M., & Goel, A. (2018). Enhanced AZIN1 RNA editing and overexpression of its regulatory enzyme ADAR1 are important prognostic biomarkers in gastric cancer. Journal of Translational Medicine, 16(1), [366]. https://doi.org/10.1186/s12967-018-1740-z