Jornal of gastric cancer, 2019. 19(3), 301-314, DOI: https://doi.org/10.5230/jgc.2019.19.e27

Exosomal miR-181b-5p Downregulation in ascites Serves as a Potential diagnostic Biomarker for Gastric Cancer-associated Malignant Ascites

Jieun Yun, Sang-Bae Han;Hong Jun Kim;Se-il Go;Won Sup Lee;Woo Kyun Bae;Sang-Hee Cho;Eun-Kee Song;Ok-Jun Lee;Hee Kyung Kim;Yaewon Yang;Jihyun Kwon;Hee Bok Chae;Ki Hyeong Lee;Hye Sook Han

Abstract

Purpose: Peritoneal carcinomatosis in gastric cancer (GC) patients results in extremelypoor prognosis. Malignant ascites samples are the most appropriate biological material touse to evaluate biomarkers for peritoneal carcinomatosis. This study identified exosomalMicroRNAs (miRNAs) differently expressed between benign liver cirrhosis-associated ascites(LC-ascites) and malignant gastric cancer-associated ascites (GC-ascites), and validated theirrole as diagnostic biomarkers for GC-ascites.

Materials and Methods: Total RNA was extracted from exosomes isolated from 165 ascitessamples (73 LC-ascites and 92 GC-ascites). Initially, microarrays were used to screen theexpression levels of 2,006 miRNAs in the discovery cohort (n=22). Subsequently, quantitativereverse tranase-polymerase chain reaction (qRT-PCR) analyses were performed tovalidate the expression levels of selected exosomal miRNAs in the training (n=70) andvalidation (n=73) cohorts. Furthermore, carcinoembryonic antigen (CEA) levels weredetermined in ascites samples.

Results: The miR-574-3p, miR-181b-5p, miR-4481, and miR-181d were significantlydownregulated 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 diagnosticperformance of CEA for GC-ascites was improved by the combined analysis of miR-181b-5pand 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 couldimprove diagnosis.

• DOI: https://doi.org/10.5230/jgc.2019.19.e27
• ISBN or ISSN: 2093-582X

• 본 연구는 질병관리본부 연구개발과제연구비를 지원받아 수행되었습니다.
• This research was supported by a fund by Research of Korea Centers for Disease Control and Prevention.