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

Zhang, Chenghao; He, Jieyu; Qi, Lin; Lü, Wei; Wang, Wanchun; Tu, Chao; Li, Zhihong

doi:10.1080/14737159.2021.1874922

Cited by 17 publications

(16 citation statements)

References 64 publications

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“…Two previous systematic reviews have performed meta-analyses on the clinicopathologic significance and prognostic value of circRNAs in osteosarcoma [ 21 , 22 ]. The latest review included 31 studies, including 22 on clinicopathologic features and 23 on survival prognosis [ 22 ]. Thus, the pooled results may be underpowered due to insufficient data.…”

Section: Discussionmentioning

confidence: 99%

“…Except for circRNAs, microRNAs and long non-coding RNAs have also shown potential diagnostic, prognostic, and therapeutic values in musculoskeletal malignancies [ 16 – 22 , 84 – 86 ]. On the other hand, evidence is being produced on non-coding RNAs being of importance in benign musculoskeletal diseases [ 87 – 90 ].…”

Section: Discussionmentioning

confidence: 99%

“…They are also involved in malignant phenotypes of osteosarcoma, such as treatment resistance and metastasis. Further quantitative analysis showed the potential of circRNAs in clinical implication as diagnostic or prognostic biomarkers [ 21 , 22 ]. However, the previous meta-analyses included a number of studies that did not analyze the relation between circRNAs and treatment response and failed to pool repeatably studied circRNAs.…”

Section: Introductionmentioning

confidence: 99%

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Clinicopathologic significance and prognostic value of circRNAs in osteosarcoma: a systematic review and meta-analysis

2021

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Background Osteosarcoma is the most prevalent malignant osseous sarcoma in children and adolescents, whose prognosis is still relatively poor nowadays. Recent studies have shown the critical function and potential clinical applications of circular RNAs (circRNAs) in osteosarcoma. Our review aimed to perform an updated meta-analysis to explore their clinicopathologic significance and prognostic value. Methods The structured literature was conducted via eight electronic databases and four gray literature sources until 20 Feb 2021 to identify eligible studies. The data was extracted directly from the articles or reconstructed based on Kaplan-Meier curves. The Newcastle-Ottawa Scale (NOS) tool was used to assess study quality. The clinicopathologic significance of circRNAs was measured through odds ratios (ORs) and their 95% confidence intervals (CIs), while the prognostic value was evaluated through hazard ratios (HRs) and their 95% CIs of overall survival (OS) and disease-free survival (DFS). Heterogeneity and publication bias were assessed. Sensitivity analyses were conducted. Subgroup analyses were performed according to study characteristics. An additional analysis was performed to investigate the relation between circ_0002052 and osteosarcoma. Results Fifty-two studies were identified, in which 38 on clinicopathologic features and 36 on survival prognosis were included in quantitative analysis. The overall study quality was moderate with a median NOS score of 5.5 stars (range 3 to 8). For clinicopathologic features, dysregulated circRNAs were related to larger tumor size (OR 2.122, 95%CI 1.418–3.175), advanced clinical stage (OR 2.847, 95%CI 2.059–3.935), and present of metastasis (OR 2.630, 95%CI 1.583–4.371). For chemotherapy, dysregulated circRNAs suggest a better response (OR 0.443, 95%CI 0.231–0.849), but a higher probability of resistance (OR 9.343, 95%CI 5.352–16.309). For survival prognosis, dysregulated circRNAs were significantly correlated with poor OS (HR 2.437, 95%CI 2.224–2.670) and DFS (HR 2.125, 95%CI 1.621–2.786). The results did not show differences among subgroups. Higher circ_0002052 expression showed a relation with poor OS (HR 3.197, 95%CI 2.054–4.976). Conclusions Our review demonstrated that abnormally expressed circRNAs have a relation with advanced clinicopathologic features and better response, but a higher probability of resistance and poor survival prognosis in osteosarcoma patients. However, more studies are encouraged to provide more robust evidence to translate circRNAs into clinical practice. Trial registration PROSPERO ID: CRD42021235031

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Clinicopathologic significance and prognostic value of circRNAs in osteosarcoma: a systematic review and meta-analysis

2021

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“…Besides, the regulatory network in osteosarcoma is still obscure, and thus no targeted therapy could be implemented, posing a significant challenge to current modalities [ 6 ]. Therefore, it is a substantial need to explore the underlying molecular biology and pathogenesis in osteosarcoma progression and to develop corresponding novel therapies to improve the prognosis of patients [ 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

Functional interplay between long non-coding RNAs and the Wnt signaling cascade in osteosarcoma

Lin

Liu

et al. 2021

Cancer Cell Int

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Osteosarcoma is a common and highly malignant bone tumor among children, adolescents and young adults. However, the underlying molecular mechanisms remain largely unexplored. LncRNAs are transcripts with no or limited protein-coding capacity in human genomes, and have been demonstrated to play crucial functions in initiation, progression, therapeutic resistance, recurrence and metastasis of tumor. Considerable studies revealed a dysregulated lncRNA expression pattern in osteosarcoma, which may act as oncogenes or suppressors to regulate osteosarcoma progression. Wnt signaling pathway is an important cascade in tumorigenesis by modulation of pleiotropic biological functions including cell proliferation, apoptosis, differentiation, stemness, genetic stability and chemoresistance. Hyperactivation or deficiency of key effectors in Wnt cascade is a common event in many osteosarcoma patients. Recently, increasing evidences have suggested that lncRNAs could interplay with component of Wnt pathway, and thereby contribute to osteosarcoma onset, progression and dissemination. In this review, we briefly summarize Wnt signaling-related lncRNAs in osteosarcoma progression, aiming to gain insights into their underlying crosstalk as well as clinical application in osteosarcoma therapeutic modalities.

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“…It is characterized by the production of osteoid tissue and immature bone mainly in the metaphysis of long bones (3). Though the prognosis of osteosarcoma has improved significantly over the past decades, outcomes for most patients remain variable, under the influence of multiple elements, for instance, the genetic and epigenetic background (4)(5)(6)(7).…”

Section: Introductionmentioning

confidence: 99%

MTHFR Polymorphism Is Associated With Severe Methotrexate-Induced Toxicity in Osteosarcoma Treatment

et al. 2021

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BackgroundPrevious studies have revealed the critical role of methylene tetrahydrofolate reductase (MTHFR) polymorphisms in response to high-dose methotrexate (MTX)-induced toxicity in osteosarcoma patients. However, the conclusions remain controversial. In this setting, we performed a meta-analysis to determine their association more precisely.MethodEligible studies were searched and screened in PubMed, Web of Science, Cochrane Library, Clinical-Trials.gov, Embase, and China National Knowledge Infrastructure (CNKI) following specific inclusion and exclusion criteria. The required information was retrieved and collected for subsequent meta-analysis. Association between MTHFR polymorphism and MTX toxicity was evaluated by odds ratios (ORs).ResultsSeven studies containing 585 patients were enrolled and analyzed in this meta-analysis. Overall, the MTX related grade 3-4 liver toxicity was significantly associated with MTHFR rs1801133 allele (T vs. C: OR=1.61, 95%CI=1.07-2.42, P=0.024), homozygote (TT vs. CC: OR=2.11, 95%CI=1.06-4.21, P=0.011), and dominant genetic model (TT/TC vs. CC: OR=3.15, 95%CI=1.30-7.60, P=0.035) in Asian population. Meanwhile, close associations between MTX mediated grade 3-4 mucositis and MTHFR rs1801133 polymorphism were identified in allele contrast (T vs. C: OR=2.28, 95%CI=1.49-3.50, P<0.001), homozygote comparison (TT vs. CC: OR=4.07, 95%CI=1.76-9.38, P=0.001), heterozygote comparison (TC vs. CC: OR=2.55, 95%CI=1.20-5.42, P=0.015), recessive genetic model (TT vs. TC/CC: OR=2.09, 95%CI=1.19-3.67, P=0.010), and dominant genetic model (TT/TC vs. CC: OR=2.97, 95%CI=1.48-5.96, P=0.002). Additionally, kidney toxicity was corelated with the heterozygote comparison (TC vs. CC: OR=2.63, 95%CI=1.31-5.29, P=0.007) of rs1801133 polymorphism.ConclusionThe MTHFR rs1801133 polymorphism was significantly associated with severer liver toxicity induced by high-dose MTX treatment in the Asian population. In the meantime, patients with MTHFR rs1801133 polymorphism were predisposed to MTX- related mucositis.

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

Cited by 17 publications

References 64 publications

Clinicopathologic significance and prognostic value of circRNAs in osteosarcoma: a systematic review and meta-analysis

Clinicopathologic significance and prognostic value of circRNAs in osteosarcoma: a systematic review and meta-analysis

Functional interplay between long non-coding RNAs and the Wnt signaling cascade in osteosarcoma

MTHFR Polymorphism Is Associated With Severe Methotrexate-Induced Toxicity in Osteosarcoma Treatment

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