Diagnostic and Prognostic Significance of Dysregulated Expression of Circular RNAs in Osteosarcoma

ABSTRACT

Objective

This study aimed to perform an updated meta-analysis to explore the clinical, diagnostic, and prognostic values of circRNAs in osteosarcoma.

Methods

: PubMed, Web of Science, EMBASE, Scopus, and Cochrane Library were systematically searched up to December 15, 2020. Eligible studies regarding the relationship between circRNAs levels and clinicopathological, diagnostic, and prognostic values in osteosarcoma were included for study.

Results

31 studies involving 1979 osteosarcoma patients were enrolled, with 22 studies on clinicopathological parameters, eleven on diagnosis, and 23 on prognosis. For clinical parameters, overexpression of oncogenic circRNAs was intimately correlated with larger tumor size, advanced Enneking stage, poor differentiation, and distant metastasis (DM). In contrast, the downregulated circRNAs showed negative correlation with Enneking stage and DM. For the diagnostic values, the summary area under the curve of circRNA for the discriminative efficacy between osteosarcoma patients and non-cancer counterparts was estimated to be 0.87, with a weighted sensitivity of 0.79, specificity of 0.81, respectively. For the prognostic significance, oncogenic circRNAs had poor overall survival (OS) and disease-free survival, while elevated expression of tumor-suppressor circRNAs were closely related to longer OS.

Conclusion

This study showed that aberrantly expressed circRNA signatures could serve as potential biomarkers in diagnosis and prognosis in osteosarcoma.

KEYWORDS:

• CircRNA
• osteosarcoma
• diagnosis
• prognosis
• survival
• biomarker

List of abbreviations

AUC, area under curve; CIs, confidence intervals; circRNAs, Circular RNAs; ceRNA, competing endogenous RNA; DM, distant metastasis; DFS, disease-free survival; HRs, hazard ratios; miRNA, microRNA; NOS, Newcastle-Ottawa Scale; ncRNAs, non-coding RNAs; OS, overall survival; ORs, odds ratios; PFS, progression-free survival; QUADAS II, Quality Assessment for Studies of Diagnostic Accuracy II; RBP, RNA-binding protein; SROC curve, summary receiver operator characteristic curve

Availability of data and materials

The data used and analyzed in the study is available from the corresponding author on reasonable request.

Authors’ contributions

C. Tu conceived and designed the study; C.H. Zhang and J.Y. He collected and assembled the data; C.H. Zhang, J.Y. He, L. Qi, L. Wan, W.C. Wang, C. Tu, Z.H. Li were involved in the analysis and interpretation of the data; C. Tu and Z.H. Li wrote the manuscript; and all authors approved the final version of the manuscript. Conception and design: CT; Collection and assembly of data: CHZ and JYH; Data analysis and interpretation: All authors; Manuscript writing: CT and ZHL; Final approval of manuscript: All authors.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. The authors declare no competing interests.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Supplemental data

Supplemental data for this paper can be accessed on the publisher’s website.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China [81902745] and Natural Science Foundation of Hunan Province, China [2018JJ3716].