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. 2022 Jan 28:11:773236.
doi: 10.3389/fonc.2021.773236. eCollection 2021.

Systematic Review With Meta-Analysis: Diagnostic, Prognostic and Clinicopathological Significance of CircRNA Expression in Renal Cancer

Wujun Wang  1   2 , Shengfang Xie  1 , Dongping Yuan  2 , Dandan He  1 , Liming Fang  1 , Fengfeng Ge  1
Affiliations

Systematic Review With Meta-Analysis: Diagnostic, Prognostic and Clinicopathological Significance of CircRNA Expression in Renal Cancer

Wujun Wang et al. Front Oncol. .

Abstract

Background: Renal cancer (RC) is one of the most common malignant tumors of the urinary system, and molecular targets for the specific diagnosis and treatment of RC have been widely explored. The purpose of this study was to systematically analyze circular RNAs (circRNAs), which may serve as novel tumor markers in terms of the diagnosis, prognosis and clinicopathological characteristics of RC.

Methods: PubMed and Web of Science were systematically searched for literature as up to July 30, 2021. All included studies were evaluated by the evaluation system, and the results were satisfactory. Hazard ratios (HRs) and odds ratios (ORs) were used to assess the association of circRNAs with diagnostic and clinicopathological indicators. The sensitivity (SEN), specificity (SPE), positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio and area under the summary receiver operating characteristic curve (AUC) were combined to evaluate the diagnostic performance of circRNAs in RC.

Results: We included 22 studies that met the criteria, including 18 that were prognostic, 4 that were diagnostic, and 12 that were clinicopathologically relevant. In terms of prognosis, we found that upregulated circRNAs were positively associated with poor overall survival in patients with RC (HR=1.63, 95% CI=1.43-1.85). In terms of diagnosis, the combined SEN, SPE and AUC of circRNAs in the diagnosis of RC were 0.82, 0.84 and 0.89 (0.86-0.91), respectively. In terms of clinicopathological features, upregulated circRNAs were associated with the Fuhrman grade (OR=0.641, 95% CI=0.471-0.873), T stage (OR=0.236, 95% CI=0.141-0.396), TNM stage (OR=0.225, 95% CI=0.158-0.321) and lymphatic metastasis (OR=0.329, 95% CI=0.193-0.560).

Conclusion: Our meta-analysis confirms that circRNAs may be candidate biomarkers for the diagnosis, prognosis, and clinicopathological indicators of RC.

Keywords: circRNA; clinicopathological; diagnostic; meta-analysis; prognostic; renal cancer.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
The PRISMA flowchart of the literature selection process.
Figure 2
Figure 2
Quality assessment by the NOS. (A) each bias risk item for each included study; (B) each bias risk item is presented as a percentage for all included studies.
Figure 3
Figure 3
Quality assessment by the QUADAS II. (A) each bias risk item for each included study; (B) each bias risk item is presented as a percentage for all included studies.
Figure 4
Figure 4
Forest plots of the (A) OS and (B) PFS/CCS/MFS/DFS of RC patients for circRNAs.
Figure 5
Figure 5
Subgroup analyses of OS for circRNAs, stratified by (A) country, (B) cut-off value, (C) sample size, (D) follow-up time, and (E) survival analysis.
Figure 6
Figure 6
Subgroup analyses of PFS/CCS/MFS/DFS for circRNAs, stratified by (A) country, (B) cut-off value, (C) sample size, (D) follow-up time, (E) survival analysis, and (F) survival outcome.
Figure 7
Figure 7
Forest plots of the combined (A) SEN, (B) SPE, (C) PLR, (D) NLR, (E) DOR, (F) ROC curve, and (G) SROC curve to illustrate the diagnosis of RC.
Figure 8
Figure 8
(A) Bivariate boxplot, (B) Deeks’ funnel plot, (C) Scatter plot, and (D) Fagan’s nomogram to illustrate the effect of circRNAs on the diagnosis of RC.
Figure 9
Figure 9
Forest plots of the clinicopathological characteristics, (A) Fuhrman grade, (B) T stage, (C) lymphatic metastasis, (D) M stage, and (E) TNM stage for circRNAs in RC.
Figure 10
Figure 10
Forest plots of the clinicopathological characteristics, (A) gender, (B) age, and (C) tumor size for circRNAs in RC.
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