Clinical significance of circulating miR-25-3p as a novel diagnostic and prognostic biomarker in osteosarcoma

Tomohiro Fujiwara, Koji Uotani, Aki Yoshida, Takuya Morita, Yutaka Nezu, Eisuke Kobayashi, Akihiko Yoshida, Takenori Uehara, Toshinori Omori, Kazuhisa Sugiu, Tadashi Komatsubara, Ken Takeda, Toshiyuki Kunisada, Machiko Kawamura, Akira Kawai, Takahiro Ochiya, Toshihumi Ozaki

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Background: Emerging evidence has suggested that circulating microRNAs (miRNAs) in body fluids have novel diagnostic and prognostic significance for patients with malignant diseases. The lack of useful biomarkers is a crucial problem of bone and soft tissue sarcomas; therefore, we investigated the circulating miRNA signature and its clinical relevance in osteosarcoma. Methods: Global miRNA profiling was performed using patient serum collected from a discovery cohort of osteosarcoma patients and controls and cell culture media. The secretion of the detected miRNAs from osteosarcoma cells and clinical relevance of serum miRNA levels were evaluated using in vitro and in vivo models and a validation patient cohort. Results: Discovery screening identified 236 serum miRNAs that were highly expressed in osteosarcoma patients compared with controls, and eight among these were also identified in the cell culture media. Upregulated expression levels of miR-17- 5p and miR-25-3p were identified in osteosarcoma cells, and these were abundantly secreted into the culture media in tumor-derived exosomes. Serum miR-25-3p levels were significantly higher in osteosarcoma patients than in control individuals in the validation cohort, with favorable sensitivity and specificity compared with serum alkaline phosphatase. Furthermore, serum miR-25-3p levels at diagnosis were correlated with patient prognosis and reflected tumor burden in both in vivo models and patients; these associations were more sensitive than those of serum alkaline phosphatase. Conclusions: Serum-based circulating miR-25-3p may serve as a noninvasive blood-based biomarker for tumor monitoring and prognostic prediction in osteosarcoma patients.

Original languageEnglish
Pages (from-to)33375-33392
Number of pages18
JournalOncotarget
Volume8
Issue number20
DOIs
Publication statusPublished - 2017

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Osteosarcoma
Biomarkers
MicroRNAs
Serum
Culture Media
Alkaline Phosphatase
Cell Culture Techniques
Exosomes
Body Fluids
Tumor Biomarkers
Tumor Burden
Sarcoma
Bone and Bones
Sensitivity and Specificity

Keywords

  • Biomarker
  • Liquid biopsy
  • MicroRNA
  • Osteosarcoma
  • Prognosis

ASJC Scopus subject areas

  • Oncology

Cite this

Clinical significance of circulating miR-25-3p as a novel diagnostic and prognostic biomarker in osteosarcoma. / Fujiwara, Tomohiro; Uotani, Koji; Yoshida, Aki; Morita, Takuya; Nezu, Yutaka; Kobayashi, Eisuke; Yoshida, Akihiko; Uehara, Takenori; Omori, Toshinori; Sugiu, Kazuhisa; Komatsubara, Tadashi; Takeda, Ken; Kunisada, Toshiyuki; Kawamura, Machiko; Kawai, Akira; Ochiya, Takahiro; Ozaki, Toshihumi.

In: Oncotarget, Vol. 8, No. 20, 2017, p. 33375-33392.

Research output: Contribution to journalArticle

Fujiwara, T, Uotani, K, Yoshida, A, Morita, T, Nezu, Y, Kobayashi, E, Yoshida, A, Uehara, T, Omori, T, Sugiu, K, Komatsubara, T, Takeda, K, Kunisada, T, Kawamura, M, Kawai, A, Ochiya, T & Ozaki, T 2017, 'Clinical significance of circulating miR-25-3p as a novel diagnostic and prognostic biomarker in osteosarcoma', Oncotarget, vol. 8, no. 20, pp. 33375-33392. https://doi.org/10.18632/oncotarget.16498
Fujiwara, Tomohiro ; Uotani, Koji ; Yoshida, Aki ; Morita, Takuya ; Nezu, Yutaka ; Kobayashi, Eisuke ; Yoshida, Akihiko ; Uehara, Takenori ; Omori, Toshinori ; Sugiu, Kazuhisa ; Komatsubara, Tadashi ; Takeda, Ken ; Kunisada, Toshiyuki ; Kawamura, Machiko ; Kawai, Akira ; Ochiya, Takahiro ; Ozaki, Toshihumi. / Clinical significance of circulating miR-25-3p as a novel diagnostic and prognostic biomarker in osteosarcoma. In: Oncotarget. 2017 ; Vol. 8, No. 20. pp. 33375-33392.
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abstract = "Background: Emerging evidence has suggested that circulating microRNAs (miRNAs) in body fluids have novel diagnostic and prognostic significance for patients with malignant diseases. The lack of useful biomarkers is a crucial problem of bone and soft tissue sarcomas; therefore, we investigated the circulating miRNA signature and its clinical relevance in osteosarcoma. Methods: Global miRNA profiling was performed using patient serum collected from a discovery cohort of osteosarcoma patients and controls and cell culture media. The secretion of the detected miRNAs from osteosarcoma cells and clinical relevance of serum miRNA levels were evaluated using in vitro and in vivo models and a validation patient cohort. Results: Discovery screening identified 236 serum miRNAs that were highly expressed in osteosarcoma patients compared with controls, and eight among these were also identified in the cell culture media. Upregulated expression levels of miR-17- 5p and miR-25-3p were identified in osteosarcoma cells, and these were abundantly secreted into the culture media in tumor-derived exosomes. Serum miR-25-3p levels were significantly higher in osteosarcoma patients than in control individuals in the validation cohort, with favorable sensitivity and specificity compared with serum alkaline phosphatase. Furthermore, serum miR-25-3p levels at diagnosis were correlated with patient prognosis and reflected tumor burden in both in vivo models and patients; these associations were more sensitive than those of serum alkaline phosphatase. Conclusions: Serum-based circulating miR-25-3p may serve as a noninvasive blood-based biomarker for tumor monitoring and prognostic prediction in osteosarcoma patients.",
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AU - Uotani, Koji

AU - Yoshida, Aki

AU - Morita, Takuya

AU - Nezu, Yutaka

AU - Kobayashi, Eisuke

AU - Yoshida, Akihiko

AU - Uehara, Takenori

AU - Omori, Toshinori

AU - Sugiu, Kazuhisa

AU - Komatsubara, Tadashi

AU - Takeda, Ken

AU - Kunisada, Toshiyuki

AU - Kawamura, Machiko

AU - Kawai, Akira

AU - Ochiya, Takahiro

AU - Ozaki, Toshihumi

PY - 2017

Y1 - 2017

N2 - Background: Emerging evidence has suggested that circulating microRNAs (miRNAs) in body fluids have novel diagnostic and prognostic significance for patients with malignant diseases. The lack of useful biomarkers is a crucial problem of bone and soft tissue sarcomas; therefore, we investigated the circulating miRNA signature and its clinical relevance in osteosarcoma. Methods: Global miRNA profiling was performed using patient serum collected from a discovery cohort of osteosarcoma patients and controls and cell culture media. The secretion of the detected miRNAs from osteosarcoma cells and clinical relevance of serum miRNA levels were evaluated using in vitro and in vivo models and a validation patient cohort. Results: Discovery screening identified 236 serum miRNAs that were highly expressed in osteosarcoma patients compared with controls, and eight among these were also identified in the cell culture media. Upregulated expression levels of miR-17- 5p and miR-25-3p were identified in osteosarcoma cells, and these were abundantly secreted into the culture media in tumor-derived exosomes. Serum miR-25-3p levels were significantly higher in osteosarcoma patients than in control individuals in the validation cohort, with favorable sensitivity and specificity compared with serum alkaline phosphatase. Furthermore, serum miR-25-3p levels at diagnosis were correlated with patient prognosis and reflected tumor burden in both in vivo models and patients; these associations were more sensitive than those of serum alkaline phosphatase. Conclusions: Serum-based circulating miR-25-3p may serve as a noninvasive blood-based biomarker for tumor monitoring and prognostic prediction in osteosarcoma patients.

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KW - Biomarker

KW - Liquid biopsy

KW - MicroRNA

KW - Osteosarcoma

KW - Prognosis

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