Search Results
As shown in Fig. 1, 83 relevant studies were obtained from the database. Among them, 46 were full-text reviews and 27 were abstract reviews. Then, 27 articles were excluded for the following reasons: 5 were not about circRNAs or CRC, 10 did not report relevant outcomes, 3 were review articles, 1 was animal data, and 8 had insufficient data. In summary, there were 19 studies[13-31] included in this study, with a total of 1307 patients, including 11 on clinical parameters, 8 on prognosis and 7 on diagnosis.
Study characteristics
The main features of this analysis are presented in Table 1 and Table 2. All studies were published between 2015 and 2019. The number of samples ranged from 40-204, and the follow-up time of patients ranged from 57 months to 123 months. As shown in Table 1, six circRNAs were identified as tumour promoters, and two circRNAs were identified as tumour suppressors. As shown in Table 2, seven articles with sensitivity, specificity, and AUC data were included for the diagnosis analysis. All studies were of great quality with the quality scores ranging from 7 to 8(Supplementary Table 1).
Clinicopathological parameters
The associations between circRNAs and the clinical features of CRC patients are shown in Table 3. There was a significant correlation between the increase in oncogenic circRNAs expression and poor clinical features(tumor size: OR=1.769, 95% CI: 1.097 -2.852 ; differentiation grade: OR=1.743, 95% CI: 1.032-2.946; TNM stage: OR=3.320, 95% CI: 1.529 -7.207; T classification: OR=3.410, 95% CI :2.088-5.567; lymph node metastasis: OR=3.357, 95% CI: 2.160-5.215; distal metastasis: OR = 4.338, 95% CI: 2.503-7.520).In addition, high expression of tumor-suppressor circRNAs were related to favorable clinical parameter (differentiation grade: OR=0.453 , 95%CI : 0.261-0.787; T classification: OR=0.553, 95%CI: 0.328-0.934; distal metastasis: OR =0.196, 95%CI: 0.077 -0.498 ). However, no notable differences were found in terms of age, gender, or tumor location.
Overall survival
As shown in Fig.2A, the elevated expression of oncogenic circRNAs was notably associated with a poor prognosis (OS: HR = 2.29, 95% Cl: 1.50–3.52, p < 0.001), and a fixed-effects model was used with no great heterogeneity (I² = 0.0%, p = 0.937). In addition, the low expression of tumour-suppressor circRNAs was related to shorter survival times (OS: HR = 0.37, 95% Cl: 0.22–0.64, p < 0.001). No great heterogeneity (I² = 0.0%, p = 0.525) was found, and a fixed-effects model was employed (Fig. 2B).
Diagnosis analysis
Fig. 3 provides the forest plot of the sensitivity and specificity of circRNAs. And the random-effects model was employed with high heterogeneity (I² = 76.15% and I2=48.29%). The pooled results showed a sensitivity of 0.83 (95% CI: 0.75-0.88) and a specificity of 0.72 (95% CI: 0.66-0.78). In addition, the summary receiver operator characteristic (SROC) curve (Fig. 4) was calculated and AUC was 0.82 (95% CI 0.78–0.85). Taken together, these results suggest that circRNAs have a good diagnostic accuracy for CRC.
Publication bias and sensitivity analysis
From the funnel plot, there was no evidence of publication bias in our study (Supplementary Figure 1). There was no obvious publication bias according to Begg's funnel plot (p = 0.213; Supplementary Figure 2) and Egger's test (p = 0.722; Supplementary Figure 3). The sensitivity analysis suggested that the results were not altered greatly when omitting studies one by one (Supplementary Figure 4). Furthermore, Deek’s funnel plot asymmetry test[32] showed no obvious publication bias(p=0.07) for the diagnosis analysis (Supplementary Figure 5).