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 language | English |
|---|---|
| Pages (from-to) | 33375-33392 |
| Number of pages | 18 |
| Journal | Oncotarget |
| Volume | 8 |
| Issue number | 20 |
| DOIs | |
| Publication status | Published - 2017 |
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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 journal › Article
}
TY - JOUR
T1 - Clinical significance of circulating miR-25-3p as a novel diagnostic and prognostic biomarker in osteosarcoma
AU - Fujiwara, Tomohiro
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.
AB - 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.
KW - Biomarker
KW - Liquid biopsy
KW - MicroRNA
KW - Osteosarcoma
KW - Prognosis
UR - http://www.scopus.com/inward/record.url?scp=85019178651&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85019178651&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.16498
DO - 10.18632/oncotarget.16498
M3 - Article
VL - 8
SP - 33375
EP - 33392
JO - Oncotarget
JF - Oncotarget
SN - 1949-2553
IS - 20
ER -