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Exosomal miRNAs from Peritoneum Lavage Fluid as Potential Prognostic Biomarkers of Peritoneal Metastasis in Gastric Cancer

Peritoneal metastasis is the most frequent type of recurrence in patients with gastric cancer (GC) and is associated with poor prognosis. Peritoneal lavage cytology, used to evaluate the risk of peritoneal metastasis, has low sensitivity. Here, we assessed the diagnostic potential of exosomal miRNA...

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Autores principales: Tokuhisa, Motohiko, Ichikawa, Yasushi, Kosaka, Nobuyoshi, Ochiya, Takahiro, Yashiro, Masakazu, Hirakawa, Kosei, Kosaka, Takashi, Makino, Hirochika, Akiyama, Hirotoshi, Kunisaki, Chikara, Endo, Itaru
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4514651/
https://www.ncbi.nlm.nih.gov/pubmed/26208314
http://dx.doi.org/10.1371/journal.pone.0130472
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author Tokuhisa, Motohiko
Ichikawa, Yasushi
Kosaka, Nobuyoshi
Ochiya, Takahiro
Yashiro, Masakazu
Hirakawa, Kosei
Kosaka, Takashi
Makino, Hirochika
Akiyama, Hirotoshi
Kunisaki, Chikara
Endo, Itaru
author_facet Tokuhisa, Motohiko
Ichikawa, Yasushi
Kosaka, Nobuyoshi
Ochiya, Takahiro
Yashiro, Masakazu
Hirakawa, Kosei
Kosaka, Takashi
Makino, Hirochika
Akiyama, Hirotoshi
Kunisaki, Chikara
Endo, Itaru
author_sort Tokuhisa, Motohiko
collection PubMed
description Peritoneal metastasis is the most frequent type of recurrence in patients with gastric cancer (GC) and is associated with poor prognosis. Peritoneal lavage cytology, used to evaluate the risk of peritoneal metastasis, has low sensitivity. Here, we assessed the diagnostic potential of exosomal miRNA profiles in peritoneal fluid for the prediction of peritoneal dissemination in GC. Total RNA was extracted from exosomes isolated from six gastric malignant ascites (MA) samples, 24 peritoneal lavage fluid (PLF) samples, and culture supernatants (CM) of two human gastric carcinoma cell lines that differ in their potential for peritoneal metastasis. Expression of exosomal miRNAs was evaluated with Agilent Human miRNA microarrays and quantitative reverse transcription polymerase chain reaction (qRT-PCR). The microarray analysis indicated a low variability in the number and signal intensity of miRNAs detected among the samples. In the six MA fluids, miR-21 showed the highest signal intensity. We identified five miRNAs (miR-1225-5p, miR-320c, miR-1202, miR-1207-5p, and miR-4270) with high expression in MA samples, the PLF of serosa-invasive GC, and the CM of a highly metastatic GC cell line; these candidate miRNA species appear to be related to peritoneal dissemination. Differential expression of miR-21, miR-320c, and miR-1225-5p was validated in the PLF of serosa-invasive and non-invasive GC by qRT-PCR and miR-21 and miR-1225-5p were confirmed to be associated with serosal invasion in GC. PLF can be used to profile the expression of exosomal miRNAs. Our findings suggest that miR-21 and miR-1225-5p may serve as biomarkers of peritoneal recurrence after curative GC resection, thus providing a novel approach to early diagnosis of peritoneal dissemination of GC.
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spelling pubmed-45146512015-07-29 Exosomal miRNAs from Peritoneum Lavage Fluid as Potential Prognostic Biomarkers of Peritoneal Metastasis in Gastric Cancer Tokuhisa, Motohiko Ichikawa, Yasushi Kosaka, Nobuyoshi Ochiya, Takahiro Yashiro, Masakazu Hirakawa, Kosei Kosaka, Takashi Makino, Hirochika Akiyama, Hirotoshi Kunisaki, Chikara Endo, Itaru PLoS One Research Article Peritoneal metastasis is the most frequent type of recurrence in patients with gastric cancer (GC) and is associated with poor prognosis. Peritoneal lavage cytology, used to evaluate the risk of peritoneal metastasis, has low sensitivity. Here, we assessed the diagnostic potential of exosomal miRNA profiles in peritoneal fluid for the prediction of peritoneal dissemination in GC. Total RNA was extracted from exosomes isolated from six gastric malignant ascites (MA) samples, 24 peritoneal lavage fluid (PLF) samples, and culture supernatants (CM) of two human gastric carcinoma cell lines that differ in their potential for peritoneal metastasis. Expression of exosomal miRNAs was evaluated with Agilent Human miRNA microarrays and quantitative reverse transcription polymerase chain reaction (qRT-PCR). The microarray analysis indicated a low variability in the number and signal intensity of miRNAs detected among the samples. In the six MA fluids, miR-21 showed the highest signal intensity. We identified five miRNAs (miR-1225-5p, miR-320c, miR-1202, miR-1207-5p, and miR-4270) with high expression in MA samples, the PLF of serosa-invasive GC, and the CM of a highly metastatic GC cell line; these candidate miRNA species appear to be related to peritoneal dissemination. Differential expression of miR-21, miR-320c, and miR-1225-5p was validated in the PLF of serosa-invasive and non-invasive GC by qRT-PCR and miR-21 and miR-1225-5p were confirmed to be associated with serosal invasion in GC. PLF can be used to profile the expression of exosomal miRNAs. Our findings suggest that miR-21 and miR-1225-5p may serve as biomarkers of peritoneal recurrence after curative GC resection, thus providing a novel approach to early diagnosis of peritoneal dissemination of GC. Public Library of Science 2015-07-24 /pmc/articles/PMC4514651/ /pubmed/26208314 http://dx.doi.org/10.1371/journal.pone.0130472 Text en © 2015 Tokuhisa et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Tokuhisa, Motohiko
Ichikawa, Yasushi
Kosaka, Nobuyoshi
Ochiya, Takahiro
Yashiro, Masakazu
Hirakawa, Kosei
Kosaka, Takashi
Makino, Hirochika
Akiyama, Hirotoshi
Kunisaki, Chikara
Endo, Itaru
Exosomal miRNAs from Peritoneum Lavage Fluid as Potential Prognostic Biomarkers of Peritoneal Metastasis in Gastric Cancer
title Exosomal miRNAs from Peritoneum Lavage Fluid as Potential Prognostic Biomarkers of Peritoneal Metastasis in Gastric Cancer
title_full Exosomal miRNAs from Peritoneum Lavage Fluid as Potential Prognostic Biomarkers of Peritoneal Metastasis in Gastric Cancer
title_fullStr Exosomal miRNAs from Peritoneum Lavage Fluid as Potential Prognostic Biomarkers of Peritoneal Metastasis in Gastric Cancer
title_full_unstemmed Exosomal miRNAs from Peritoneum Lavage Fluid as Potential Prognostic Biomarkers of Peritoneal Metastasis in Gastric Cancer
title_short Exosomal miRNAs from Peritoneum Lavage Fluid as Potential Prognostic Biomarkers of Peritoneal Metastasis in Gastric Cancer
title_sort exosomal mirnas from peritoneum lavage fluid as potential prognostic biomarkers of peritoneal metastasis in gastric cancer
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4514651/
https://www.ncbi.nlm.nih.gov/pubmed/26208314
http://dx.doi.org/10.1371/journal.pone.0130472
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