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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