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Table 2 Prognostic, association, and diagnostic evaluation of miR-212

From: MiR-212 value in prognosis and diagnosis of cancer and its association with patient characteristics: a systematic review and meta-analysis

A. Prognostic evaluation

Sub-group

N of studies

N of patients

Pooled hazard ratio (HR) (95% CI)

p-value

Heterogeneity

Fixed

Random

I2

p-value

Overall survival

 Overall

18

1479

2.190 (1.895–2.532)

2.081 (1.593–2.717)

 < 0.001

68.9

 < 0.001

 Publication year

0.226

77.07

 < 0.001

  < 2017

5

478

2.234 (1.719–2.904)

2.234 (1.719–2.904)

 < 0.001

0.00

0.947

  2017

5

418

1.715 (1.277–2.303)

1.611 (0.811–3.200)

0.174

79.7

0.001

  > 2017

8

583

2.463 (1.986–3.055)

2.284 (1.433–3.641)

0.001

77

 < 0.001

 Sample size

0.021

71.15

 < 0.001

  < 75

9

515

1.703 (1.336–2.171)

1.722 (1.002–2.961)

0.049

79.2

 < 0.001

  > 75

9

964

2.518 (2.102–3.016)

2.498 (2.042–3.055)

 < 0.001

18.1

0.282

 Cancer type

 < 0.001

0.00

0.756

  HCC

5

434

2.145 (1.681–2.736)

2.145 (1.681–2.736)

 < 0.001

0.00

0.974

  CRC

3

293

2.508 (1.622–3.878)

2.508 (1.622–3.878)

 < 0.001

0.00

0.805

  PDAC

2

86

0.408 (0.241–0.691)

0.408 (0.241–0.691)

0.001

0.00

0.785

  Gastric

2

181

3.474 (2.450–4.927)

3.216 (1.545–6.696)

0.002

75.6

0.043

 Cancer type

 < 0.001

0.28

0.438

  PDAC

2

86

0.408 (0.241–0.691)

0.408 (0.241–0.691)

0.001

0.00

0.785

  Others

16

1393

2.514 (2.162–2.923)

2.514 (2.162–2.923)

 < 0.001

0.00

0.660

 Stage

0.484

80.14

 < 0.001

  I-IV

12

902

2.121 (1.779–2.528)

1.944 (1.304–2.898)

0.001

79.3

 < 0.001

  Others

6

577

2.346 (1.816–3.031)

2.346 (1.816–3.031)

 < 0.001

0.00

0.942

 Follow-up period

0.484

80.14

 < 0.001

  <  = 60

11

848

2.074 (1.735–2.478)

1.833 (1.214–2.767)

0.004

80.3

 < 0.001

  > 60

7

631

2.438 (1.900–3.129)

2.438 (1.900–3.129)

 < 0.001

0.00

0.825

 Cut-off point

0.389

78.91

 < 0.001

  Median

13

1068

2.412 (2.035–2.859)

2.320 (1.713–3.141)

 < 0.001

66.5

 < 0.001

  Others

5

411

1.693 (1.282–2.235)

1.568 (0.915–2.690)

0.102

71.9

0.007

 Specimen

0.097

73.08

 < 0.001

  Tissue

16

1289

1.973 (1.684–2.311)

1.933 (1.473–2.537)

 < 0.001

64.3

 < 0.001

  Serum

2

190

3.763 (2.626–5.393)

3.549 (1.996–6.308)

 < 0.001

56.4

0.130

 MiR-212 type

0.836

80.34

 < 0.001

  miR-212

14

1127

2.189 (1.861–2.574)

2.001 (1.435–2.791)

 < 0.001

75.2

 < 0.001

  miR-212-3p

3

227

2.228 (1.558–3.188)

2.259 (1.525–3.344)

 < 0.001

12.8

0.318

  miR-212-5p

1

125

2.066 (0.974–4.383)

 

–

 

–

Adjusted overall survival

 Overall

5

540

2.121 (1.561–2.881)

2.121 (1.561–2.881)

 < 0.001

0.00

0.618

Disease-free survival

 Overall

5

559

2.812 (2.138–3.700)

2.812 (2.138–3.700)

 < 0.001

0.00

0.892

Adjusted disease-free survival

 Overall

2

181

2.059 (1.360–3.115)

2.278 (1.085–4.786)

0.030

63.1

0.100

Recurrence-free survival

 Overall

2

143

1.842 (1.240–2.737)

1.842 (1.240–2.737)

0.002

0.00

0.742

B. Association evaluation

Sub-group

N of studies

N of patients

Pooled odds ratio (OR) (95% CI)

p-value

Heterogeneity

Fixed

Random

I2

p-value

Gender (male/female)

13

1026

1.012 (0.766–1.337)

0.993 (0.729–1.353)

0.931

15

0.293

Age (old/young)

18

1394

0.819 (0.652–1.028)

0.819 (0.652–1.028)

0.085

0.00

0.899

Metastasis (yes/no)

4

228

2.521 (1.417–4.486)

3.110 (0.624–15.508)

0.166

86.2

 < 0.001

Lymphatic metastasis (yes/no)

3

195

4.614 (1.958–10.873)

4.529 (0.576–35.588)

0.151

62.3

0.071

Tumor size (large/small)

14

1096

1.344 (1.038–1.741)

1.195 (0.635–2.249)

0.580

82.1

 < 0.001

Tumor size ([> 5 or ≥ 5]/[< 5 or ≤ 5])

8

712

1.296 (0.942–1.783)

1.455 (0.630–3.364)

0.380

84.7

 < 0.001

T stage (III-IV/I-II)

2

222

0.792 (0.401–1.563)

0.515 (0.082–3.212)

0.477

79.7

0.027

TNM stage (III-IV/I-II)

12

786

2.844 (2.057–3.932)

2.719 (1.674–4.415)

 < 0.001

51.3

0.020

Differentiation (others/poor)

4

306

0.894 (0.557–1.435)

0.894 (0.556–1.438)

0.642

0.67

0.389

Hepatitis B virus (present/absent)

5

434

0.916 (0.576–1.456)

0.955 (0.545–1.673)

0.711

28.6

0.231

Serum AFP level (high/low)

5

434

2.319 (1.559–3.451)

2.319 (1.559–3.451)

 < 0.001

0.00

0.646

Serum AFP level (> 200/ ≤ 200)

2

163

1.620 (0.862–3.047)

1.620 (0.862–3.047)

0.134

0.00

0.642

Serum AFP level (≥ 400/ < 400)

3

271

2.933 (1.759–4.889)

2.933 (1.759–4.889)

 < 0.001

0.00

0.892

Number of tumor nodules (≥ 2/1)

3

264

1.216 (0.718–2.060)

1.275 (0.536–3.031)

0.583

62.4

0.070

Cirrhosis (present/absent)

5

434

1.111 (0.748–1.649)

1.118 (0.728–1.718)

0.602

15.3

0.317

Venous infiltration (present/absent)

3

271

1.859 (1.145–3.019)

1.859 (1.145–3.019)

0.012

0.00

0.735

Edmondson-Steiner grade (III-IV/I-II)

4

354

1.757 (1.129–2.735)

1.757 (1.129–2.735)

0.013

0.00

0.532

Venous invasion (positive/negative)

4

320

2.351 (1.460–3.785)

1.772 (0.629–4.996)

0.279

76.9

0.005

Distant metastasis (M1/M0)

3

283

1.401 (0.723–2.714)

0.726 (0.102–5.183)

0.750

85.7

0.001

Histological grade (poor, moderate-well)

2

225

1.231 (0.667–2.273)

1.080 (0.415–2.808)

0.505

45.3

0.176

C. Diagnostic evaluation

Youden index

Sub-group

N

Sen

Spe

PLR

NLR

DOR

RDOR,

p-value

Overall

 

 Overall

8

0.72 (0.67–0.76)

0.79 (0.75–0.83)

3.25 (1.85–5.71)

0.38 (0.23–0.63)

10.69 (3.64–31.35)

 I2, p-value

 

91.5, < 0.001

88.1, < 0.001

84.9, < 0.001

90.1, < 0.001

87.3, < 0.001

Publication year

3.26 (0.00–1.8E5), 0.754

 < 2017

5

0.63 (0.55–0.70)

0.79 (0.72–0.85)

3.01 (1.35–6.69)

0.49 (0.29–0.81)

8.69 (2.28–33.08)

 > 2017

3

0.78 (0.72–0.84)

0.79 (0.74–0.84)

3.64 (1.43–9.22)

0.28 (0.10–0.82)

13.41 (1.89–95.26)

Ethnicity

0.29 (0.00–3.7E3), 0.707

 Caucasian

3

0.72 (0.63–0.79)

0.74 (0.66–0.81)

2.45 (0.91–6.54)

0.28 (0.08–1.07)

12.92 (1.41–118.79)

 Asian

5

0.72 (0.66–0.77)

0.81 (0.76–0.85)

3.88 (1.88–8.01)

0.40 (0.21–0.77)

10.80 (2.78–41.86)

Sample size

0.41 (0.00–1.6E2), 0756

 < 50

5

0.64 (0.56–0.72)

0.84 (0.78–0.89)

3.84 (1.58–9.29)

0.46 (0.28–0.77)

9.85 (3.11–31.19)

 > 50

3

0.76 (0.70–0.81)

0.75 (0.69–0.81)

2.93 (1.14–7.56)

0.30 (0.10–0.95)

10.14 (1.24–83.07)

Sample type

1.05 (0.00–4.2E2), 0.986 (serum vs. others)

 Serum

3

0.83 (0.78–0.88)

0.75 (0.69–0.80)

3.07 (1.24–7.58)

0.23 (0.07–0.79)

13.90 (1.79–108.13)

 Plasma

2

0.72 (0.61–0.82)

0.82 (0.74–0.89)

3.92 (2.09–7.34)

0.28 (0.05–1.63)

14.26 (1.63–124.80)

 Tissue

2

0.40 (0.26–0.55)

0.94 (0.83–0.99)

6.26 (1.98–19.80)

0.65 (0.52–0.83)

9.72 (2.63–35.90)

Index of union

Overall

 

 Overall

8

0.74 (0.70–0.78)

0.73 (0.69–0.78)

2.38 (1.48–3.83)

0.37 (0.22–0.64)

7.49 (2.62–21.44)

 I2, p-value

 

87.1, < 0.001

87.6, < 0.001

85.2, < 0.001

87.2, < 0.001

88.8, < 0.001

Publication year

6.78 (0.00–6.3E5), 0.631

 < 2017

5

0.66 (0.59–0.73)

0.71 (0.64–0.78)

1.84 (1.10–3.08)

0.49 (0.29–0.84)

4.67 (1.52–14.33)

 > 2017

3

0.81 (0.75–0.86)

0.75 (0.69–0.80)

3.13 (1.30–7.58)

0.27 (0.09–0.81)

12.11 (1.65–89.01)

Ethnicity

0.14 (0.00–2.6E3), 0.570

 Caucasian

3

0.68 (0.59–0.76)

0.76 (0.67–0.83)

2.53 (0.88–7.22)

0.36 (0.13–1.02)

10.20 (1.26–82.66)

 Asian

5

0.77 (0.72–0.82)

0.73 (0.67–0.78)

2.45 (1.35–4.44)

0.37 (0.18–0.75)

6.95 (1.78–27.18)

Sample size

0.56 (0.00–3.4E3), 0.844

 < 50

5

0.71 (0.63–0.78)

0.71 (0.64–0.77)

1.94 (1.17–3.22)

0.45 (0.27–0.77)

5.30 (1.75–16.09)

 > 50

3

0.76 (0.70–0.81)

0.75 (0.69–0.81)

2.93 (1.14–7.56)

0.30 (0.10–0.95)

10.14 (1.24–83.07)

Sample type

0.90 (0.00–5.5E3), 0.970

 Serum

3

0.81 (0.75–0.86)

0.76 (0.69–0.81)

3.06 (1.20–7.81)

0.27 (0.08–0.84)

11.94 (1.49–95.54)

 Plasma

2

0.79 (0.68–0.88)

0.73 (0.64–0.81)

3.12 (1.06–9.14)

0.26 (0.06–1.22)

12.28 (1.04–144.29)

 Tissue

2

0.54 (0.39–0.69)

0.71 (0.56–0.83)

2.65 (0.44–16.16)

0.63 (0.45–0.89)

4.06 (0.59–27.69)

  1. The pooled hazard ratio (OR) of survival analysis showing mortality in low miR-212 patients compared to high miR-212 patients (A). The pooled odds ratio (OR) showing the association between patient characteristics with the incidence of low miR-212 level (B). Diagnostic variables in cancer diagnosis using miR-212 level (C), and meta-regression analysis of diagnostic value based on study preferences
  2. N number, Fixed fixed-effects model, Random random-effects model, Sen sensitivity, Spe specificity, PLR positive likelihood ratio, NLR negative likelihood ratio, DOR diagnostic odds ratio, RDOR meta-regression relative diagnostic odds ratio
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