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Table 1 List of miRNAs of interest with age-adjusted FD ≥4 between the three studied cohorts in the pilot phase (upregulated FC ≥4, downregulated FC ≤ -4)

From: Profiling microRNAs in individuals at risk of progression to rheumatoid arthritis

 

HC

CCP

VERA

CCP vs. HC

VERA vs. HC

CCP to VERA (within progressors)

 

miR

dCt median (IQR)

dCt median (IQR)

dCt median (IQR)

FD between medians

FD between medians

Median (IQR) ddCt

Median FC

Number upregulated (/12)

miR-16

-6.3 (-7.1, -6.0)

-7.1 (-7.6, -7.0)

-7.6 (-8.2, -7.4)

1.7

2.4

-0.4 (-1.1, -0.1)

1.3

10

miR-18a

0.1 (-0.8, 1.3)

1.3 (0.3, 2.0)

-0.1 (-1.0, 0.4)

-2.4

1.1

-1.6 (-2.0, -1.0)

3.1

10

miR-19a

-0.9 (-1.6, 1.0)

-2.4 (-2.8, -1.9)

-3.2 (-3.5, -2.8)

2.9

5.0

-0.6 (-1.7, 0.1)

1.5

9

miR-21

-2.8 (-4.1, -2.5)

-3.8 (-4.4, -3.3)

-4.3 (-4.8, -4.1)

2.0

2.7

-0.7 (-1.2, -0.2)

1.6

9

miR-22

4.2 (0.5, 4.8)

3.0 (1.5, 5.1)

0.9 (0.6, 1.5)

2.2

9.4

-2.1 (-3.6, -1.5)

4.3

12

miR-26b

-1.4 (-3.0, 0.2)

-3.1 (-3.4, -1.8)

-3.6 (-4.2, -2.8)

3.3

4.7

-0.7 (-2.3, -0.3)

1.7

10

miR-34a

-0.2 (-2.1, 0.8)

-0.1 (-0.3, 1.0)

-0.6 (-2.1, 0.2)

-1.1

1.3

-0.1 (-0.9, 0.3)

1.1

6

miR-101

2.5 (1.7, 3.2)

1.6 (1.3, 1.8)

0.4 (-0.3, 0.9)

1.9

4.3

-1.1 (-1.9, -0.6)

2.1

11

miR-132

-1.6 (-2.0, -1.4)

-1.7 (-2.1, -1.6)

-2.5 (-2.7, -2.2)

1.0

1.8

-0.8 (-1.1, -0.3)

1.7

11

miR-142-3p

-2.3 (-4.5, -1.3)

-4.4 (-4.5, -3.8)

-5.0 (-5.2, -4.5)

4.2

6.2

-0.4 (-1.1, -0.3)

1.4

10

miR-142-5p

3.9 (2.9, 5.7)

3.0 (2.4, 5.5)

1.7 (1.5, 4.3)

1.9

4.7

-1.3 (-1.4, -0.3)

2.4

10

miR-146a

-7.3 (-7.5, -6.5)

-7.1 (-7.6, -7.0)

-7.5 (-7.7, -7.3)

-1.2

1.1

-0.5 (-0.8, 0.2)

1.4

8

miR-155

-0.9 (-2.3, 1.5)

0.1 (-0.5, 1.1)

-0.5 (-0.7, -0.3)

-2.1

-1.4

-0.3 (-1.3, 0.1)

1.2

8

miR-195

-2.5 (-3.0, -1.6)

-0.4 (-3.4, 0.2)

-2.9 (-4.2, -0.5)

-4.6

1.3

-1.1 (-2.0, -0.5)

2.1

11

miR-197

-3.5 (-3.3, -1.3)

0.6 (-1.5, 2.9)

0.6 (-2.5, 2.2)

-16.8

-16.5

-0.6 (-2.7, 1.3)

1.5

7

miR-203

2.3 (1.8, 3.0)

3.0 (2.1, 3.0)

2.9 (2.6, 3.4)

-1.5

-1.5

0.0 (-0.4, 0.6)

1.0

6

miR-210

3.9 (0.1, 5.0)

3.1 (2.2, 3.4)

1.5 (1.1, 1.8)

1.8

5.1

-1.8 (-2.9, -0.3)

3.4

10

miR-223

-9.3 (-9.6, -8.8)

-9.9 (-9.9, -9.6)

-10.3 (-10.4, -10.0)

1.5

2.0

-0.4 (-0.6, 0.2)

1.3

6/9a

miR-361

-0.1 (-1.1, 1.1)

2.1 (-0.5, 2.5)

0.6 (-0.2, 0.7)

-4.7

-1.7

-1.5 (-2.1, -1.0)

2.9

11

miR-374d

-2.2 (-3.4, -2.1)

-3.2 (-3.7, -2.0)

-4.1 (-4.3, -3.9)

2.0

3.8

-0.6 (-1.0, -0.4)

1.5

12

miR-382

-0.7 (-1.2, 0.5)

1.4 (0.9, 2.7)

-0.1 (-1.2, 0.5)

-4.1

-1.5

-2.0 (-2.8, -0.8)

4.1

11

miR-454d

-1.3 (-2.8, 0.2)

-2.3 (-3.2, -0.1)

-3.0 (-3.3, -1.3)

1.9

3.3

-0.5 (-1.1, -0.2)

1.4

10

miR-486-3p

4.3 (2.5, 5.6)

4.9 (2.5, 6.2)

3.5 (3.1, 4.3)

-1.5

1.8

-2.0 (-3.1, 0.2)

4.1

9

miR-520c-3p

2.3 (0.3, 2.9)

-0.4 (-1.6, 2.4)

-1.1 (-1.4, 0.5)

6.3

10.6

0.3 (-1.7, 0.6)

-1.3

5

miR-579c

4.2 (3.5, 5.0)

3.5 (3.1, 3.7)

2.4 (1.8, 2.9)

1.6

3.6

-1.2 (-1.7, -0.3)

2.2

11

miR-590-3P

5.2 (2.9, 5.8)

3.2 (2.3, 3.9)

2.4 (2.2, 3.1)

3.9

6.9

-0.9 (-1.1, 0.2)

1.9

8

miR-590-5p

1.2 (0.7, 1.4)

-0.4 (-1.2, -0.2)

-1.3 (-1.6, -0.7)

3.0

5.6

-0.5 (-1.1, -0.3)

1.4

10

miR-598

3.7 (3.1, 4.3)

2.8 (2.5, 3.6)

1.5 (1.4, 1.9)

1.8

4.6

-1.2 (-1.7, -0.8)

2.2

12

miR-628-5p

3.0 (-8.4, 7.9)

-7.2 (-8.3, 3.9)

-2.9 (-7.8, 2.2)

1174.6

61.3

0.4 (-1.6, 1.7)

-1.3

5

miR-15b#

9.9 (2.6, 11.4)

6.2 (5.6, 8.4)

4.0 (2.0, 4.4)

13.3b

58.5b

-2.6 (-4.0, -1.8)

6.1b

11/11

miR-335#

6.1 (5.6, 8.3)

6.5 (5.2, 8.1)

4.2 (3.9, 5.1)

-1.4b

3.6b

-1.9 (-3.9, -1.0)

3.8b

12

  1. microRNA (miRNA) highlighted in bold in matched samples (CCP-VERA) met criteria of median fold change (FC) ≥4 and ≥75% consistent dysregulation. If fold difference (FD) was < 1, FD = -1/FD. Estimates for each cohort were obtained at the mean age (52 years)
  2. dCt delta cycle threshold, HC healthy controls
  3. aFor 3 patients, Ct values at follow up were extremely low (all ≈ 2, compared to ≈ 14 for the rest); these 3 values were considered to be inaccurate and in a conservative approach were excluded from analysis
  4. bIn these miRNAs, Ct was > 32 for some healthy controls and CCP+ patients at baseline. As a result, the calculated fold differences and changes may not be accurate; therefore, these genes were not deemed to have fulfilled our criteria for dysregulation, but were retained for further investigation in the validation cohort because the calculated FCs were near or above our cutoff, and all progressors showed consistent dysregulation
  5. cIn this miRNA mean FC was >4; miR-579 FC 4.27 (although median FC <4), furthermore consistent dysregulation was seen in 11/12 patients. As custom cards had capacity for 31 miRNAs to be evaluated these two miRNAs were selected as potentially important
  6. dThe original selection of miR-454 (FD 4.1 between HC-VERA) and miR-374 (FD 4.6 between HC-VERA) from the pilot phase was based on unadjusted between-group differences; following age-adjustment they no longer met our criteria
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Arthritis Research & Therapy

ISSN: 1478-6362

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