Skip to main content
Erschienen in: International Journal of Clinical Oncology 8/2019

20.05.2019 | Original Article

A four serum-miRNA panel serves as a potential diagnostic biomarker of osteosarcoma

verfasst von: Congwei Huang, Qinjue Wang, Shengshan Ma, Yang Sun, Ashley Shane Vadamootoo, Chengzhe Jin

Erschienen in: International Journal of Clinical Oncology | Ausgabe 8/2019

Einloggen, um Zugang zu erhalten

Abstract

Background

Osteosarcoma (OS) is the most common malignant bone tumor in young adults and adolescents with approximately 3 million new cases annually. Due to the lack of sensitive and specific diagnostic biomarkers, although OS patients are curable after surgical resection, many patients suffer from metastasis or recurrence. This study aimed to investigate whether circulating microRNAs (miRNAs) could serve as biomarkers for the diagnosis of OS.

Materials and methods

Healthy individuals and OS patients enrolled in this study came from Nanjing First Hospital. First, candidate miRNAs were selected by integrated analysis of two GEO datasets and a publicly available miRNA dataset. The expression of these miRNAs in tissues and serum samples were subsequently examined through qRT-PCR. The diagnostic utility of these differential miRNAs was examined by using receiver operating characteristic (ROC) curve analysis. Finally, the potential signaling pathways associated with candidate miRNAs were searched through online tools.

Results

Four miRNAs (miR-487a, miR-493-5p, miR-501-3p and miR-502-5p) were selected to further investigate their diagnostic potential for OS. We discovered miR-487a, miR-493-5p, miR-501-3p and miR-502-5p were upregulated in OS tissues and serums. Besides, miR-487a, miR-493-5p, miR-501-3p and miR-502-5p in peripheral blood of OS patients were tumor-derived. The area under the ROC curve (AUC) was 0.83 (95% CI 0.71–0.97) for miR-487a, 0.79 (95% CI 0.66–0.93) for miR-493-5p, 0.82 (95% CI 0.68–0.95) for miR-501-3p, 0.83 (95% CI 0.72–0.95) for miR-502-5p, and 0.89 (95% CI 0.78–1.0) for miRNAs combination.

Conclusion

Circulating miR-487a, miR-493-5p, miR-501-3p and miR-502-5p were novel potential diagnostic biomarkers of OS.
Literatur
1.
Zurück zum Zitat Ma O, Cai WW, Zender L et al (2009) MMP13, Birc2 (cIAP1), and Birc3 (cIAP2), amplified on chromosome 9, collaborate with p53 deficiency in mouse osteosarcoma progression. Cancer Res 69:2559–2567CrossRefPubMedPubMedCentral Ma O, Cai WW, Zender L et al (2009) MMP13, Birc2 (cIAP1), and Birc3 (cIAP2), amplified on chromosome 9, collaborate with p53 deficiency in mouse osteosarcoma progression. Cancer Res 69:2559–2567CrossRefPubMedPubMedCentral
2.
Zurück zum Zitat Kansara M, Teng MW, Smyth MJ et al (2014) Translational biology of osteosarcoma. Nat Rev Cancer 14:722–735CrossRef Kansara M, Teng MW, Smyth MJ et al (2014) Translational biology of osteosarcoma. Nat Rev Cancer 14:722–735CrossRef
3.
Zurück zum Zitat Yang J, Zhang W (2013) New molecular insights into osteosarcoma targeted therapy. Curr Opin Oncol 25:398–406CrossRefPubMed Yang J, Zhang W (2013) New molecular insights into osteosarcoma targeted therapy. Curr Opin Oncol 25:398–406CrossRefPubMed
4.
Zurück zum Zitat Bielack SS, Kempf-Bielack B, Delling G et al (2002) Prognostic factors in high-grade osteosarcoma of the extremities or trunk: an analysis of 1,702 patients treated on neoadjuvant cooperative osteosarcoma study group protocols. J Clin Oncol 20:776–790CrossRefPubMed Bielack SS, Kempf-Bielack B, Delling G et al (2002) Prognostic factors in high-grade osteosarcoma of the extremities or trunk: an analysis of 1,702 patients treated on neoadjuvant cooperative osteosarcoma study group protocols. J Clin Oncol 20:776–790CrossRefPubMed
5.
Zurück zum Zitat Gianferante DM, Mirabello L, Savage SA (2017) Germline and somatic genetics of osteosarcoma - connecting aetiology, biology and therapy. Nat Rev Endocrinol 13:480–491CrossRefPubMed Gianferante DM, Mirabello L, Savage SA (2017) Germline and somatic genetics of osteosarcoma - connecting aetiology, biology and therapy. Nat Rev Endocrinol 13:480–491CrossRefPubMed
6.
Zurück zum Zitat Fabian MR, Sonenberg N, Filipowicz W (2010) Regulation of mRNA translation and stability by microRNAs. Annu Rev Biochem 79:351–379CrossRef Fabian MR, Sonenberg N, Filipowicz W (2010) Regulation of mRNA translation and stability by microRNAs. Annu Rev Biochem 79:351–379CrossRef
7.
Zurück zum Zitat Mitchell PS, Parkin RK, Kroh EM et al (2008) Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci USA 105:10513–10518CrossRef Mitchell PS, Parkin RK, Kroh EM et al (2008) Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci USA 105:10513–10518CrossRef
8.
Zurück zum Zitat Bekris LM, Leverenz JB (2015) The biomarker and therapeutic potential of miRNA in Alzheimer's disease. Neurodegener Dis Manag 5:61–74CrossRefPubMed Bekris LM, Leverenz JB (2015) The biomarker and therapeutic potential of miRNA in Alzheimer's disease. Neurodegener Dis Manag 5:61–74CrossRefPubMed
9.
Zurück zum Zitat Li SP, Su HX, Zhao D et al (2016) Plasma miRNA-506 as a Prognostic Biomarker for Esophageal Squamous Cell Carcinoma. Med Sci Monit 22:2195–2201CrossRefPubMedPubMedCentral Li SP, Su HX, Zhao D et al (2016) Plasma miRNA-506 as a Prognostic Biomarker for Esophageal Squamous Cell Carcinoma. Med Sci Monit 22:2195–2201CrossRefPubMedPubMedCentral
10.
Zurück zum Zitat Tanase C, Albulescu R, Codrici E et al (2015) Circulating biomarker panels for targeted therapy in brain tumors. Future Oncol 11:511–524CrossRefPubMed Tanase C, Albulescu R, Codrici E et al (2015) Circulating biomarker panels for targeted therapy in brain tumors. Future Oncol 11:511–524CrossRefPubMed
11.
Zurück zum Zitat Guo L, Luo C, Fan J et al (2015) Serum miRNA profiling identifies miR-150/30a as potential biomarker for workers with damaged nerve fibers from carbon disulfide. Ind Health 53:38–47CrossRefPubMed Guo L, Luo C, Fan J et al (2015) Serum miRNA profiling identifies miR-150/30a as potential biomarker for workers with damaged nerve fibers from carbon disulfide. Ind Health 53:38–47CrossRefPubMed
12.
Zurück zum Zitat Lian F, Cui Y, Zhou C et al (2015) Identification of a plasma four-microRNA panel as potential noninvasive biomarker for osteosarcoma. PLoS ONE 10:e0121499CrossRefPubMedPubMedCentral Lian F, Cui Y, Zhou C et al (2015) Identification of a plasma four-microRNA panel as potential noninvasive biomarker for osteosarcoma. PLoS ONE 10:e0121499CrossRefPubMedPubMedCentral
13.
Zurück zum Zitat Nonaka R, Nishimura J, Kagawa Y et al (2014) Circulating miR-199a-3p as a novel serum biomarker for colorectal cancer. Oncol Rep 32:2354–2358CrossRefPubMed Nonaka R, Nishimura J, Kagawa Y et al (2014) Circulating miR-199a-3p as a novel serum biomarker for colorectal cancer. Oncol Rep 32:2354–2358CrossRefPubMed
14.
Zurück zum Zitat Maciejak A, Kostarska-Srokosz E, Gierlak W et al (2018) Circulating miR-30a-5p as a prognostic biomarker of left ventricular dysfunction after acute myocardial infarction. Sci Rep 8:9883CrossRefPubMedPubMedCentral Maciejak A, Kostarska-Srokosz E, Gierlak W et al (2018) Circulating miR-30a-5p as a prognostic biomarker of left ventricular dysfunction after acute myocardial infarction. Sci Rep 8:9883CrossRefPubMedPubMedCentral
15.
16.
Zurück zum Zitat Kelly AD, Haibe-Kains B, Janeway KA et al (2013) MicroRNA paraffin-based studies in osteosarcoma reveal reproducible independent prognostic profiles at 14q32. Genome Med 5:2CrossRefPubMedPubMedCentral Kelly AD, Haibe-Kains B, Janeway KA et al (2013) MicroRNA paraffin-based studies in osteosarcoma reveal reproducible independent prognostic profiles at 14q32. Genome Med 5:2CrossRefPubMedPubMedCentral
17.
18.
Zurück zum Zitat Zhu T, Gao W, Chen X et al (2017) A pilot study of circulating MicroRNA-125b as a diagnostic and prognostic biomarker for epithelial ovarian cancer. Int J Gynecol Cancer 27:3–10CrossRefPubMed Zhu T, Gao W, Chen X et al (2017) A pilot study of circulating MicroRNA-125b as a diagnostic and prognostic biomarker for epithelial ovarian cancer. Int J Gynecol Cancer 27:3–10CrossRefPubMed
19.
Zurück zum Zitat Li C, Li JF, Cai Q et al (2013) MiRNA-199a-3p: A potential circulating diagnostic biomarker for early gastric cancer. J Surg Oncol 108:89–92CrossRefPubMed Li C, Li JF, Cai Q et al (2013) MiRNA-199a-3p: A potential circulating diagnostic biomarker for early gastric cancer. J Surg Oncol 108:89–92CrossRefPubMed
20.
Zurück zum Zitat Zhou G, Lu M, Chen J et al (2015) Identification of miR-199a-5p in serum as noninvasive biomarkers for detecting and monitoring osteosarcoma. Tumour Biol 36:8845–8852CrossRefPubMed Zhou G, Lu M, Chen J et al (2015) Identification of miR-199a-5p in serum as noninvasive biomarkers for detecting and monitoring osteosarcoma. Tumour Biol 36:8845–8852CrossRefPubMed
21.
Zurück zum Zitat Xu J, Pan X, Hu Z (2018) MiR-502 mediates esophageal cancer cell TE1 proliferation by promoting AKT phosphorylation. Biochem Biophys Res Commun 501:119–123CrossRefPubMed Xu J, Pan X, Hu Z (2018) MiR-502 mediates esophageal cancer cell TE1 proliferation by promoting AKT phosphorylation. Biochem Biophys Res Commun 501:119–123CrossRefPubMed
22.
Zurück zum Zitat Sanches JGP, Xu Y, Yabasin IB et al (2018) miR-501 is upregulated in cervical cancer and promotes cell proliferation, migration and invasion by targeting CYLD. Chem Biol Interact 285:85–95CrossRefPubMed Sanches JGP, Xu Y, Yabasin IB et al (2018) miR-501 is upregulated in cervical cancer and promotes cell proliferation, migration and invasion by targeting CYLD. Chem Biol Interact 285:85–95CrossRefPubMed
23.
Zurück zum Zitat Zhao J, Xu T, Wang F et al (2017) miR-493-5p suppresses hepatocellular carcinoma cell proliferation through targeting GP73. Biomed Pharmacother 90:744–751CrossRefPubMed Zhao J, Xu T, Wang F et al (2017) miR-493-5p suppresses hepatocellular carcinoma cell proliferation through targeting GP73. Biomed Pharmacother 90:744–751CrossRefPubMed
24.
Zurück zum Zitat Chang RM, Xiao S, Lei X et al (2017) miRNA-487a promotes proliferation and metastasis in hepatocellular carcinoma. Clin Cancer Res 23:2593–2604CrossRefPubMed Chang RM, Xiao S, Lei X et al (2017) miRNA-487a promotes proliferation and metastasis in hepatocellular carcinoma. Clin Cancer Res 23:2593–2604CrossRefPubMed
Metadaten
Titel
A four serum-miRNA panel serves as a potential diagnostic biomarker of osteosarcoma
verfasst von
Congwei Huang
Qinjue Wang
Shengshan Ma
Yang Sun
Ashley Shane Vadamootoo
Chengzhe Jin
Publikationsdatum
20.05.2019
Verlag
Springer Singapore
Erschienen in
International Journal of Clinical Oncology / Ausgabe 8/2019
Print ISSN: 1341-9625
Elektronische ISSN: 1437-7772
DOI
https://doi.org/10.1007/s10147-019-01433-x

Weitere Artikel der Ausgabe 8/2019

International Journal of Clinical Oncology 8/2019 Zur Ausgabe

Mehr Lebenszeit mit Abemaciclib bei fortgeschrittenem Brustkrebs?

24.05.2024 Mammakarzinom Nachrichten

In der MONARCHE-3-Studie lebten Frauen mit fortgeschrittenem Hormonrezeptor-positivem, HER2-negativem Brustkrebs länger, wenn sie zusätzlich zu einem nicht steroidalen Aromatasehemmer mit Abemaciclib behandelt wurden; allerdings verfehlte der numerische Zugewinn die statistische Signifikanz.

ADT zur Radiatio nach Prostatektomie: Wenn, dann wohl länger

24.05.2024 Prostatakarzinom Nachrichten

Welchen Nutzen es trägt, wenn die Strahlentherapie nach radikaler Prostatektomie um eine Androgendeprivation ergänzt wird, hat die RADICALS-HD-Studie untersucht. Nun liegen die Ergebnisse vor. Sie sprechen für länger dauernden Hormonentzug.

Das sind die führenden Symptome junger Darmkrebspatienten

Darmkrebserkrankungen in jüngeren Jahren sind ein zunehmendes Problem, das häufig längere Zeit übersehen wird, gerade weil die Patienten noch nicht alt sind. Welche Anzeichen Ärzte stutzig machen sollten, hat eine Metaanalyse herausgearbeitet.

„Überwältigende“ Evidenz für Tripeltherapie beim metastasierten Prostata-Ca.

22.05.2024 Prostatakarzinom Nachrichten

Patienten mit metastasiertem hormonsensitivem Prostatakarzinom sollten nicht mehr mit einer alleinigen Androgendeprivationstherapie (ADT) behandelt werden, mahnt ein US-Team nach Sichtung der aktuellen Datenlage. Mit einer Tripeltherapie haben die Betroffenen offenbar die besten Überlebenschancen.

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.