Ratios of miRNAs in Peritoneal Exosomes are Useful Biomarkers to Predict Tumor Response to Intraperitoneal Chemotherapy in Patients with Peritoneal ... View Full Text


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Article Info

DATE

2020-08-17

AUTHORS

Hideyuki Ohzawa, Yuki Kimura, Akira Saito, Hironori Yamaguchi, Hideyo Miyato, Yasunaru Sakuma, Hisanaga Horie, Yoshinori Hosoya, Alan Kawarai Lefor, Naohiro Sata, Joji Kitayama

ABSTRACT

BackgroundRepeat intraperitoneal (IP) chemotherapy has been successfully used for treatment of peritoneal metastases (PM) from gastric cancer (GC). Exosomes play important roles not only in tumor progression but also in chemoresistance via transfer of microRNAs (miRNAs). However, there is little evidence of an effect of miRNAs in peritoneal exosomes on chemosensitivity of peritoneal lesions.MethodsIn 74 patients with advanced GC who underwent staging laparoscopy, exosomes were isolated from peritoneal fluid and expression levels of miR-21-5p, miR-223-3p, and miR-29b-3p determined using TaqMan Advanced miRNA assays. In 43 patients with PM treated with combination chemotherapy, S-1 plus Oxaliplatin together with IP Paclitaxel, the relationship between their relative expression levels and outcomes was examined.ResultsThe ratios of miR-21-5p/miR-29b-3p and miR-223-3p/miR-29b-3p were significantly upregulated in patients with PM, especially in patients with high serum CA125 levels. They showed a mild association with Peritoneal Cancer Index (PCI) score and ascites. More impressively, the ratios were significantly higher in 16 patients with progression of PM within 1 year compared with 27 patients with an excellent tumor response (miR-21-5p/miR-29b-3p: median 17.49, range 1.83–50.90 vs. median 4.64, range 0.40–38.96, p = 0.0015, miR-223-3p/miR-29b-3p: median 1.02, range 0.23–25.85 vs. median 0.21, range 0.01–50.07, p = 0.0006). Overall survival of patients with high miR-21/miR-29b or miR-223/miR-29b ratios was significantly worse than in patients with low ratios (p = 0.0117, p = 0.0021).ConclusionsThe ratios of miRNAs in peritoneal exosome correlate with survival of the patients with PM from GC and suggest the possibility that they modify the chemosensitivity against IP chemotherapy. More... »

PAGES

5057-5064

References to SciGraph publications

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  • Identifiers

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    http://scigraph.springernature.com/pub.10.1245/s10434-020-09007-2

    DOI

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    27 schema:description BackgroundRepeat intraperitoneal (IP) chemotherapy has been successfully used for treatment of peritoneal metastases (PM) from gastric cancer (GC). Exosomes play important roles not only in tumor progression but also in chemoresistance via transfer of microRNAs (miRNAs). However, there is little evidence of an effect of miRNAs in peritoneal exosomes on chemosensitivity of peritoneal lesions.MethodsIn 74 patients with advanced GC who underwent staging laparoscopy, exosomes were isolated from peritoneal fluid and expression levels of miR-21-5p, miR-223-3p, and miR-29b-3p determined using TaqMan Advanced miRNA assays. In 43 patients with PM treated with combination chemotherapy, S-1 plus Oxaliplatin together with IP Paclitaxel, the relationship between their relative expression levels and outcomes was examined.ResultsThe ratios of miR-21-5p/miR-29b-3p and miR-223-3p/miR-29b-3p were significantly upregulated in patients with PM, especially in patients with high serum CA125 levels. They showed a mild association with Peritoneal Cancer Index (PCI) score and ascites. More impressively, the ratios were significantly higher in 16 patients with progression of PM within 1 year compared with 27 patients with an excellent tumor response (miR-21-5p/miR-29b-3p: median 17.49, range 1.83–50.90 vs. median 4.64, range 0.40–38.96, p = 0.0015, miR-223-3p/miR-29b-3p: median 1.02, range 0.23–25.85 vs. median 0.21, range 0.01–50.07, p = 0.0006). Overall survival of patients with high miR-21/miR-29b or miR-223/miR-29b ratios was significantly worse than in patients with low ratios (p = 0.0117, p = 0.0021).ConclusionsThe ratios of miRNAs in peritoneal exosome correlate with survival of the patients with PM from GC and suggest the possibility that they modify the chemosensitivity against IP chemotherapy.
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    34 ConclusionsThe ratio
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    36 IP paclitaxel
    37 TaqMan Advanced miRNA Assays
    38 advanced gastric cancer
    39 ascites
    40 assays
    41 association
    42 biomarkers
    43 cancer
    44 chemoresistance
    45 chemosensitivity
    46 chemotherapy
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    48 correlates
    49 effect
    50 effects of miRNAs
    51 evidence
    52 excellent tumor response
    53 exosomes
    54 expression levels
    55 fluid
    56 gastric cancer
    57 high miR-21
    58 high serum CA125 levels
    59 important role
    60 index score
    61 intraperitoneal chemotherapy
    62 laparoscopy
    63 lesions
    64 levels
    65 little evidence
    66 low ratio
    67 metastasis
    68 miR
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    70 miRNA assays
    71 miRNAs
    72 microRNAs
    73 mild association
    74 outcomes
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    76 oxaliplatin
    77 paclitaxel
    78 patients
    79 peritoneal cancer index score
    80 peritoneal exosomes
    81 peritoneal fluid
    82 peritoneal lesions
    83 peritoneal metastasis
    84 possibility
    85 progression
    86 ratio
    87 relationship
    88 relative expression levels
    89 response
    90 role
    91 scores
    92 serum CA125 levels
    93 staging laparoscopy
    94 survival
    95 transfer
    96 transfer of microRNAs
    97 treatment
    98 tumor progression
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    100 useful biomarker
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