Table 1.
Summary of evidence credibility assessment of 34 unique meta-analyses of observational studies investigating the associations between risk factors and CRC metastasis
| Population | Outcome | Risk factor | Risk factor prevalence | Effect size (95% CI) | Evidence classification |
|---|---|---|---|---|---|
| Histopathological risk factor | |||||
| pT1 CRC | Lymph node metastasis in pT1 CRC | Vascular invasion | 330/1731 = 19% | 2.73 (1.98–3.78) | Convincing |
| pT1 CRC | Lymph node metastasis in pT1 CRC | Lymphatic invasion | 906/3347 = 27% | 6.78 (5.29–8.69) | Highly suggestive |
| pT1 CRC | Lymph node metastasis in pT1 CRC | Tumor budding | 2401/10,128 = 24% | 6.39 (5.23–7.80) | Highly suggestive |
| CRC | Lymph node metastasis in CRC | Tumor budding | 1955/6739 = 29% | 4.96 (3.97–6.19) | Highly suggestive |
| Rectal cancer | Lymph node metastasis in rectal cancer | Tumor size > 1 cm | 203/348 = 58% | 6.76 (3.25–14.04) | Highly suggestive |
| pT1 CRC | Lymph node metastasis in pT1 CRC | Lymphovascular invasion | 340/1695 = 20% | 4.81 (3.14–7.36) | Suggestive |
| pT1 CRC | Lymph node metastasis in pT1 CRC patients who underwent additional surgeries after an endoscopic resection | Lymphovascular invasion | 91/313 = 29% | 5.29 (2.34–11.98) | Suggestive |
| pT1 CRC | Lymph node metastasis in pT1 CRC | Poor differentiation | 94/2722 = 4% | 5.61 (2.90–10.83) | Suggestive |
| Rectal cancer | Lymph node metastasis in rectal cancer | Muscularis properia invasion | 122/322 = 38% | 5.08 (2.32–11.11) | Suggestive |
| pT1 CRC | Lymph node metastasis in pT1 CRC | Submucosal invasion ≥ 1 mm | 2389/2922 = 82% | 2.95 (1.39–6.27) | Weak |
| Small rectal NETs | Lymph node metastasis in small rectal NETs treated by local excision | Lymphovascular invasion | 104/517 = 20% | 5.02 (1.16–21.72) | Weak |
| Rectal cancer | Lymph node metastasis in rectal cancer | Central depression | 32/76 = 42% | 3.00 (2.10–4.28) | Weak |
| Rectal cancer | Synchronous metastasis in rectal cancer | MRI-detected extramural vascular invasion (mrEMVI) | 212/804 = 26% | 5.65 (2.12–15.05) | Weak |
| Small rectal NETs | Lymph node metastasis in small rectal NETs treated by local excision | Lymphatic invasion | 73/493 = 15% | 5.54 (0.02–1752.46) | No association |
| Rectal cancer | Lymph node metastasis in rectal cancer | Vascular invasion | 46/168 = 27% | 5.86 (0.77–44.62) | No association |
| Small rectal NETs | Lymph node metastasis in small rectal NETs treated by local excision | Vascular invasion | 75/211 = 36% | 3.63 (0.05–268.57) | No association |
| pT1 CRC | Lymph node metastasis in pT1 CRC patients who underwent additional surgeries after an endoscopic resection | Poor or moderate differentiation | 122/209 = 58% | 3.77 (1.12–123.16) | No association |
| Biomarker | |||||
| CRC | Lymph node metastasis in CRC | Downregulated E-cadherin expression | 829/1573 = 53% | 0.49 (0.34–0.72) | Highly suggestive |
| CRC | Hepatic metastasis (distant) in CRC | Circulating tumor cells | 103/310 = 33% | 6.38 (2.67–15.26) | Suggestive |
| CRC | Lymph node metastasis in CRC | Low MUC2 expression level | 613/1335 = 46% | 1.42 (1.19–1.69) | Suggestive |
| CRC | Distant metastasis in CRC | Downregulated E-cadherin expression | 509/1027 = 50% | 0.45 (0.23–0.91) | Weak |
| CRC | Lymph node metastasis in CRC | Circulating tumor cells | 797/1802 = 44% | 1.62 (1.17–2.23) | Weak |
| CRC | Lymph node metastasis in CRC | p16 protein expression | 482/800 = 60% | 0.50 (0.30–0.84) | Weak |
| CRC | Distant metastasis in CRC | Cyclin D1 overexpression | 952/1515 = 63% | 0.60 (0.36–0.99) | Weak |
| CRC | Distant metastasis in CRC | β-catenin overexpression in the nucleus | 283/531 = 53% | 0.48 (0.29–0.79) | Weak |
| CRC | Lymph node metastasis in CRC | CD147 expression | 603/815 = 74% | 1.41 (0.39–5.01) | No association |
| CRC | Distant metastasis in CRC | CD147 expression | 405/538 = 75% | 2.32 (1.34E−06 to 4.03E+06) | No association |
| CRC | Lymph node metastasis in CRC | CD133 expression | 550/1629 = 34% | 1.15 (0.82–1.62) | No association |
| CRC | Distant metastasis in CRC | CD133 expression | 300/1064 = 28% | 1.54 (0.39–6.09) | No association |
| CRC | Lymph node metastasis in CRC | HER-2 immunohistochemical expression | 440/1289 = 34% | 1.90 (0.90–4.02) | No association |
| Genetic risk factor | |||||
| CRC | Lymph node metastasis in CRC | BRAF mutation | 736/1142 = 64% | 0.75 (0.49–1.14) | No association |
| CRC | Lymph node metastasis in CRC | RASSF1A promoter methylation | 100/184 = 54% | 1.61 (0.16–16.16) | No association |
| CRC | Distant metastasis in CRC | RASSF1A promoter methylation | 153/417 = 37% | 2.57 (0.64–10.24) | No association |
| Demographic risk factor | |||||
| pT1 CRC | Lymph node metastasis in pT1 CRC | Female gender | 465/1329 = 35% | 2.23 (0.78–6.42) | No association |
Abbreviation: CI confidence interval, CRC colorectal cancer, NET neuroendocrine tumor