Journal of Gastric Cancer

The Korean Gastric Cancer Association (대한위암학회)
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Exosomal miR-181b-5p Downregulation in Ascites Serves as a Potential Diagnostic Biomarker for Gastric Cancer-associated Malignant Ascites

  • Yun, Jieun (Department of Pharmaceutical Engineering, College of Science Engineering, Cheongju University) ;
  • Han, Sang-Bae (College of Pharmacy, Chungbuk National University) ;
  • Kim, Hong Jun (Department of Internal Medicine, Gyeongsang National University School of Medicine) ;
  • Go, Se-il (Department of Internal Medicine, Gyeongsang National University School of Medicine) ;
  • Lee, Won Sup (Department of Internal Medicine, Gyeongsang National University School of Medicine) ;
  • Bae, Woo Kyun (Department of Internal Medicine, Chonnam National University Hwasun Hospital) ;
  • Cho, Sang-Hee (Department of Internal Medicine, Chonnam National University Hwasun Hospital) ;
  • Song, Eun-Kee (Department of Internal Medicine, Chonbuk National University Medical School) ;
  • Lee, Ok-Jun (Department Pathology, Chungbuk National University Hospital) ;
  • Kim, Hee Kyung (Department of Internal Medicine, Chungbuk National University Hospital) ;
  • Yang, Yaewon (Department of Internal Medicine, Chungbuk National University Hospital) ;
  • Kwon, Jihyun (Department of Internal Medicine, Chungbuk National University Hospital) ;
  • Chae, Hee Bok (Department of Internal Medicine, Chungbuk National University Hospital) ;
  • Lee, Ki Hyeong (Department of Internal Medicine, Chungbuk National University Hospital) ;
  • Han, Hye Sook (Department of Internal Medicine, Chungbuk National University Hospital)
  • Received : 2019.06.18
  • Accepted : 2019.08.11
  • Published : 2019.09.30
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Abstract

Purpose: Peritoneal carcinomatosis in gastric cancer (GC) patients results in extremely poor prognosis. Malignant ascites samples are the most appropriate biological material to use to evaluate biomarkers for peritoneal carcinomatosis. This study identified exosomal MicroRNAs (miRNAs) differently expressed between benign liver cirrhosis-associated ascites (LC-ascites) and malignant gastric cancer-associated ascites (GC-ascites), and validated their role as diagnostic biomarkers for GC-ascites. Materials and Methods: Total RNA was extracted from exosomes isolated from 165 ascites samples (73 LC-ascites and 92 GC-ascites). Initially, microarrays were used to screen the expression levels of 2,006 miRNAs in the discovery cohort (n=22). Subsequently, quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) analyses were performed to validate the expression levels of selected exosomal miRNAs in the training (n=70) and validation (n=73) cohorts. Furthermore, carcinoembryonic antigen (CEA) levels were determined in ascites samples. Results: The miR-574-3p, miR-181b-5p, miR-4481, and miR-181d were significantly downregulated in the GC-ascites samples compared to the LC-ascites samples, and miR-181b-5p showed the best diagnostic performance for GC-ascites (area under the curve [AUC]=0.798 and 0.846 for the training and validation cohorts, respectively). The diagnostic performance of CEA for GC-ascites was improved by the combined analysis of miR-181b-5p and CEA (AUC=0.981 and 0.946 for the training and validation cohorts, respectively). Conclusions: We identified exosomal miRNAs capable of distinguishing between non-malignant and GC-ascites, showing that the combined use of miR-181b-5p and CEA could improve diagnosis.

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References

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