Serum-Derived microRNAs as Prognostic Biomarkers in Osteosarcoma: A Meta-Analysis.

Huan Luo,Chunhua Song,Xiao Wang,Peng Wang,Jianying Zhang,Hua Ye,Jitian Li,Jianxiang Shi,Liping Dai

doi:10.3389/fgene.2020.00789

Abstract

Recent reports suggest that microRNAs (miRNAs) may serve as prognostic biomarkers in osteosarcoma. Due to osteosarcoma's early metastasis and poor prognosis, it is very important to find novel prognostic biomarkers for improving osteosarcoma's prognosis. Herein we propose a meta-analysis for serum miRNA's prognostic value in osteosarcoma. In this study, the literature available from PubMed, Web of Science, Embase, and Cochrane Library databases was reviewed. The pooled hazard ratios (HRs) with their 95% confidence intervals (CIs) were calculated to evaluate miRNAs prognostic values. A total of 20 studies investigating serum miRNAs were included in this meta-analysis; the initial terminal point of these reports included overall survival (OS), progression-free survival (PFS), disease-free survival (DFS), and recurrence-free survival (RFS). For prognostic meta-analyses, the pooled HR for terminal events of higher expression of miRNAs and lower expression of miRNAs were 5.68 (95% CI 4.73–6.82, P < 0.05) and 3.78 (95% CI 3.27–4.37, P < 0.05), respectively. Additionally, subgroup analyses were conducted based on the analysis methods applied and clinicopathological features reported. In the pooled analyses, the miRNA expression levels are associated with poor prognosis according to both univariate and multivariate analyses. Furthermore, serum miRNAs (miRNA-195, miRNA-27a, miRNA-191, miRNA-300, miRNA-326, miRNA-497, miRNA-95-3p, miRNA-223, miRNA-491-5p, miRNA-124, miRNA-101, miRNA-139-5p, miRNA-194) were associated with poor OS and found to be closely correlated with clinical stage and distant metastasis in osteosarcoma. The results illustrate that low or high expression of these specific miRNAs are both potentially useful as prognostic serum biomarkers in osteosarcoma, and miRNAs (miRNA-195, miRNA-27a, miRNA-191, miRNA-300, miRNA-326, miRNA-497, miRNA-95-3p, miRNA-223, miRNA-491-5p, miRNA-124, miRNA-101, miRNA-139-5p, miRNA-194) may indicate clinical stage and metastasis in this form of cancer.

Highlights

METHODSPatient survival in osteosarcoma has improved in recent decades
MiRNAs that are stable in serum or plasma, or in other biological samples, may have potential utility as diagnostic or prognostic biomarkers in different cancers (Calin and Croce, 2006; EsquelaKerscher and Slack, 2006; Mitchell et al, 2008; Zhou et al, 2016). These findings show that miRNAs warrant attention as potential novel biomarkers for diagnosis or prognosis in osteosarcoma
Osteosarcoma is the common malignant bone tumor (Kansara et al, 2014) and extensive progress has been made in the development of effective therapies (Bielack et al, 2002; Collins et al, 2013), patient prognosis remains unsatisfactory

Summary

Introduction

Patient survival in osteosarcoma has improved in recent decades. Metastasis and recurrence are common challenges in refractory osteosarcoma, that worsen patient prognosis (Bielack et al, 2002). The highly malignant nature of osteosarcoma, as well as its high rates of recurrence and lung metastasis represent strong concerns (Jones et al, 2012; Ogawa et al, 2013). Histological examination of the biopsy specimens is preferred for the diagnosis or prognostic evaluation of osteosarcoma. Such invasive tests may be burdensome when monitoring the progression of the disease, and the accuracy of diagnosis and prognostic evaluation may vary because of differences in sample collection and personnel. It is essential to develop novel approaches for the timely diagnosis of osteosarcoma in order to achieve better prognosis (Gu et al, 2014)

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Results

Conclusion