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Table 4 Methylation panels investigated in plasma or serum from OC and controls for early diagnosis of OC, including information on methods, methylation frequency, and performance

From: Early diagnosis of ovarian cancer based on methylation profiles in peripheral blood cell-free DNA: a systematic review

Methylation panel

Author (et al.)

Method

Case/control

Meth OC

Meth control

Sensitivity % (95% CI)

Specificity % (95% CI)

APC,APKinase, BRCA1, p14ARF, p16INK4a, RASSF1A

de Caceres [18]

MSP

50/10b/20h (T)

41/50

0/10b

0/20h

82.0 (68.6–91.4)

100* (88.4–100)

SOX, PAX1, LMX1A, SFRP1, SFRP2, SFRP5

Su [19]

MSP

26/20b (T)

19/26*

9/20*

73.1 (52.2–88.4)

55.0 (31.5–76.9)

SOX, PAX1, SFRP1

Su [19]

MSP

26/20b (T)

19/26*

5/20*

73.1 (52.2–88.4)

75.0 (50.9–91.3)

BRCA1, HIC1, PAX5, PGR, THBS1

Melnikov [20]

MSRE PCR/microarray

33/33h (T)

28/33*

13/33*

85.1 (68.1–94.9)

61.1 (42.1–77.1)

CALCA, EP300, RASSF1A

Liggett [24]

MSRE PCR/microarray

30/30h (T)

27/30*

4/30*

90.0 (73.5–97.9)

86.7 (69.3–96.2)

PGR, RASSF1A

Liggett [24]

MSRE PCR/microarray

30/30b (T)

22/30*

6/30*

73.3 (54.1–87.7)

80.0 (61.4–92.3)

APC, CDH1, OPCML, RASSF1A, RUNX3, SFRP5, TFPI2

Zhang [27]

MSP, Nested multiplex

87/53b (T)

39/29b (V)

78/87

36/39

5/53

5/29

89.7 (81.3–95.2)

92.3 (79.1–98.4)

90.6 (79.3–96.9)

82.8 (64.2–94.2)

OPCML, RUNX3, TFPI2

Wang [30]

MSP, Nested multiplex

71/43b/80h (T)

64/71

11/123*

90.1 (80.7–95.9)

91.1 (84.6–95.5)

COL23A1, C2CD4D, WNT6

Widschwendter [34]

Targeted NGS

29/119b/21h (T)

48/154b/41h (V)

12/29

28/48

13/140

16/195

41.4 (23.5–61.1)

58.3 (43.2–72.4)

90.7 (84.6–95.0)

91.8 (87.0–95.2)

CDH1, PAX1, PTEN, RASSF1

Dvorská [36]

Pyrosequencing

33//9h (T)

30/33*

4/9*

91.0 (75.7–98.1)

56.0 (21.2–86.3)

Panel of 103,456 distinct regions and 1,116,720 CpGs

Liu [11]

Targeted NGS

27/1521h (T)

12/610h (V)

26/27

12/12

3/1521*

4/610*

96.0 (81.0–99.9)

100 (73.5–100)

99.8 (99.4–100)

99.3 (98.3–99.8)

HIC1, HOXA9

Singh [39]

Real-time qMSP

45/25h (T)

40/45

0/25

88.9 (76.0–96.3)

100 (86.3–100)

HIC1, HOXA9

Singh [42]

Real-time qMSP, Multiplex

45/25h â–  (T)

40/45

0/25

88.9 (76.0–96.3)

100 (86.3–100)

HOXA9, SOX1

Singh [42]

Real-time qMSP, Multiplex

45/25h â–  (T)

30/45

1/25

66.7 (51.1–80.0)

96.0 (79.7–99.9)

HIC1, SOX1

Singh [42]

Real-time qMSP, Multiplex

45/25h â–  (T)

36/45

1/25

80.0 (65.4–90.4)

96.0 (79.7–99.9)

AGRN, BCAT1, CAPN2, CDO1, CELF2, FAIM2, GPRIN1, GYPC, RIPPLY3, SRC, SIM2

Marinelli [44]

TELQAS

91/91h (T)

72/91*

4/91*

79.0 (69.3–86.9)

96.0 (89.1–98.8)

  1. 95% exact confidence intervals (CI) have been calculated for all methylation panels
  2. b benign, CI confidence intervals, h healthy, Meth methylated, MSP methylation-specific PCR, MSRE methylation-sensitive restriction enzyme, N/A not available, PCR polymerase chain reaction, qMSP quantitative methylation-specific PCR, TELQAS Target Enrichment Long-probe, Quantitative Amplified Signal, T training/test cohort, V validation cohort
  3. *Extrapolated calculations based on available data
  4. â– Reuse of data from Singh et al. [39]