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Table 6 Cross-assessment of the same outcomes with their corresponding risk factors and predictors

From: Risk factors and risk prediction models for colorectal cancer metastasis and recurrence: an umbrella review of systematic reviews and meta-analyses of observational studies

Overlapping outcomes Risk factor Risk factor prevalence Effect size (95% CI)a Credibility assessment Risk predictor Effect size (95% CI)b Model performance
CRC metastasis
 Lymph node metastasis in pT1 CRC Vascular invasion 330/1731 = 19% 2.73 (1.98–3.78) Convincing Vascular invasion 8.45 (4.56–15.66) AUC 0.812 (0.770–0.855); Hosmer–Lemeshow test: p = 0.737 (55)
Submucosal invasion ≥ 1 mm 2389/2922 = 82% 2.95 (1.39–6.27) Weak Submucosal invasion ≥ 1 mm 2.14 (1.19–3.86)
Tumor budding 2401/10,128 = 24% 6.39 (5.23–7.80) Highly suggestive Tumor budding 1.70 (1.03–2.80)
     Histologic grade 7.89 (2.89–21.52)
Tumor differentiation 94/2722 = 4% 5.61 (2.90–10.83) Suggestive Tumor differentiation 11.77 (0.77–179.83) AUC 0.90 (0.81–0.99) (49)
Lymphatic invasion 906/3347 = 27% 6.78 (5.29–8.69) Highly suggestive Infiltrative growth pattern 31.91 (2.37–428.36)
Lymphovascular invasion 340/1695 = 20% 4.81 (3.14–7.36) Suggestive Lymphoid infiltrate 28.75 (2.13–388.37)
Gender 465/1329 = 35% 2.23 (0.78–6.42) No association Sessile morphology 4.88 (0.81–29.3)
 Lymph node metastasis in CRC Tumor budding 1955/6739 = 29% 4.96 (3.97–6.19) Highly suggestive CT-reported lymph node status 1.69 (1.05–2.75) C statistic 0.736 (0.759–0.766); Hosmer–Lemeshow test: p = 0.916 (52)
Downregulated E-cadherin expression 829/1573 = 53% 0.49 (0.34–0.72) Highly suggestive Radiomics signature 5.48 (3.03–9.91)
Low MUC2 expression level 613/1335 = 46% 1.42 (1.19–1.69) Suggestive CEA 1.71 (1.04–2.83)
Circulating tumor cells 797/1802 = 44% 1.62 (1.17–2.23) Weak    
p16 protein expression 482/800 = 60% 0.50 (0.30–0.84) Weak    
CD147 expression 603/815 = 74% 1.41 (0.39–5.01) No association    
CD133 expression 550/1629 = 34% 1.15 (0.82–1.62) No association    
HER-2 immunohistochemical expression 440/1289 = 34% 1.90 (0.90–4.02) No association    
BRAF mutation 736/1142 = 64% 0.75 (0.49–1.14) No association    
RASSF1A promoter methylation 100/184 = 54% 1.61 (0.16–16.16) No association    
 Hepatic metastasis in CRC Circulating tumor cells 103/310 = 33% 6.38 (2.67–15.26) Suggestive Duke B/C NA Sensitivity 0.74, specificity 0.62 (50)
ALP NA
Sex/gender NA
 Distant metastasis in CRC Downregulated E-cadherin expression 509/1027 = 50% 0.45 (0.23–0.91) Weak AJCC stage 1.27 (0.25–6.38) AUC 0.80 (0.67–0.93); calibration plot (56)
Cyclin D1 overexpression 952/1515 = 63% 0.60 (0.36–0.99) Weak MiR25/MiR339 2.92 (0.98–8.64)
β-catenin overexpression in the nucleus 283/531 = 53% 0.48 (0.29–0.79) Weak Age at surgery 1.10 (0.20–6.03)
CD147 expression 405/538 = 75% 2.32 (1.34E−06 to 4.03E+06) No association Sex/gender 1.40 (0.46–4.28)
CD133 expression 300/1064 = 28% 1.54 (0.39–6.09) No association    
RASSF1A promoter methylation 153/417 = 37% 2.57 (0.64–10.24) No association    
CRC recurrence
 Overall recurrence in CRC Tumor budding 802/2773 = 29% 5.50 (3.65–8.29) Highly suggestive AJCC stage NA AUC 0.921 (0.869–0.972); calibration plot (65)
Extranodal extension (ENE) 376/877 = 43% 2.07 (1.65–2.61) Highly suggestive Tumor differentiation NA
PTGS2 (COX-2) 787/1516 = 52% 2.78 (1.76–4.40) Suggestive Gene signature NA
Absence of peritoneal free tumor cells in pre-resection 524/593 = 88% 0.38 (0.16–0.91) Weak    
Absence of peritoneal free tumor cells in post-resection 214/252 = 85% 0.07 (0.02–0.21) Weak    
Underweight 2752/17,636 = 16% 1.13 (1.05–1.21) Weak    
Obese 6362/21,246 = 30% 1.07 (1.02–1.13) Weak    
Overweight 13,225/28,109 = 47% 1.00 (0.96–1.05) No association    
Diabetes 429/4979 = 9% 1.26 (0.70–2.30) No association    
  1. Abbreviations: ALP alkaline phosphatase, AUC area under the curve, BMI body mass index, CEA carcinoembryonic antigen, CI confidence interval, CRC colorectal cancer, NA non-available, miRNA microRNA
  2. aEffect size (95% CI), effect size from the umbrella review
  3. bEffect size (95% CI), effect size from the risk prediction models