Exosomal miR-181b-5p Downregulation in Ascites Serves as a Potential Diagnostic Biomarker for Gastric Cancer-associated Malignant Ascites
- Author:
Jieun YUN
1
;
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
Author Information
- Publication Type:Original Article
- Keywords: Ascites; Biomarkers; Exosomes; Gastric cancer; MicroRNA
- MeSH: Ascites; Biomarkers; Carcinoembryonic Antigen; Carcinoma; Cohort Studies; Diagnosis; Down-Regulation; Exosomes; Humans; Liver; MicroRNAs; Prognosis; RNA; Stomach Neoplasms
- From:Journal of Gastric Cancer 2019;19(3):301-314
- CountryRepublic of Korea
- Language:English
- 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.
