From: Blood-based DNA methylation as biomarker for breast cancer: a systematic review
Gene | Author, year [ref] | Sample | Assay (value) | Case no./control no. | Case age/control age (y)b | Meth (case) | Meth (control) | p value | Main findings |
---|---|---|---|---|---|---|---|---|---|
RASSF1A | Kloten V, 2013 [58] | Serum | MS-PCR (%) | 136/135 | 33–86/33–86 | 47.1 | 25.9 | 0.004 | Higher frequency of methylated RASSF1A was observed in eight studies. Studies by Zmetakova I et al. and Brooks JD et al. reported no significant differences in methylation of RASSF1A between cases and controls |
 | Zmetakova I, 2013 [42] | Plasma | Pyrosequencing (mean ± SD) | 34/50 | 41–90/20–78 | 2.85 ± 3.13 | 4.02 ± 6.62 | 0.404 | |
 | Ahmed IA, 2010 [55] | Serum | MSP (%) | 26/12 | 35–73/35–73 | 69 | <10 | – | |
 | Brooks JD, 2010 [56]d | Serum | QMSP (%) | 50/99 | 52/51.8 | 22 | 17.2 | >0.05 | |
 | Kim JH, 2010 [57] | Serum | QMSP (%) | 119/125 | 51/51 | 32.8 | 4.8 | 0.004 | |
 | Yazici H, 2009 [46]d | Plasma | MSP (%) | 61/39 | na/na | 18 | 5 | – | |
 | Hoque M, 2006 [44] | Plasma | QMSP (%) | 47/38 | 44.9/37.3 | 32 | 5 | 0.002 | |
 | Van der Auwera I, 2009 [52] | Serum | QMSP (%) | 79/19 | 62/39 | 35 | 0 | 0.002 | |
 | Papadopoulou E, 2006 [45] | Plasma | Methylight (%) | 50/14 | na/na | 26 | 0 | <0.05 | |
 | Dulaimi E, 2004 [50] | Serum | MSP (%) | 34/20 | 57.4/57.4 | 56 | 0 | <0.05c | |
APC | Swellam M, 2015 [59] | Serum | MS-PCR (%) | 121/66 | 43/40 | 93.4 | 0 | <0.0001 | Five out of these seven studies reported higher frequency of methylated APC in BC patients. Studies by Zmetakova I et al. and Brooks JD et al. reported no significant differences in methylation of APC between cases and controls. |
 | Zmetakova I, 2013 [42] | Plasma | Pyrosequencing (mean ± SD) | 34/50 | 41–90/20–78 | 4.41 ± 7.81 | 2.53 ± 1.56 | 0.06 | |
 | Radpour R, 2011 [47] | Plasma | EpiTyper assay (mean) | 36/30 | 67/na | 0.39b | 0.19b | <0.0001 | |
 | Brooks JD, 2010 [56]d | Serum | QMSP (%) | 49/96 | 52/51.8 | 2 | 4.2 | >0.05 | |
 | Hoque M, 2006 [44] | Plasma | QMSP (%) | 47/38 | 44.9/37.3 | 17 | 0 | 0.008 | |
 | Van der Auwera I, 2009 [52] | Serum | QMSP (%) | 79/19 | 62/39 | 29 | 5 | 0.03 | |
 | Dulaimi E, 2004 [50] | Serum | MSP (%) | 34/20 | 57.4/57.4 | 29 | 0 | <0.05c | |
ESR1 | Zmetakova I, 2013 [42] | Plasma | Pyrosequencing (mean ± SD) | 34/50 | 41–90/20–78 | 4.18 ± 4.07 | 5.24 ± 4.33 | 0.338 | Only one study (Matinez-Galan, J) reported higher methylation levels of ESR1 in BC patients. Others observed no significant methylation differences. |
 | Zurita M, 2010 [54] | Serum | QMSP (%) | 77/34 | na/na | 0.005b | 0.085b | >0.05 | |
 | Van der Auwera I, 2009 [52] | Serum | QMSP (%) | 79/19 | 62/39 | 20 | 10.5 | 0.33 | |
 | Martinez-Galan J, 2008 [51] | Serum | MSP (%) | 106/74 | 58/42 | 0.11b | 0.02b | 0.011 | |
RARB | Swellam M, 2015 [59] | Serum | MS-PCR (%) | 121/66 | 43/40 | 95.9 | 0 | <0.0001 | Higher frequency of methylated RARB was observed except the study conducted by Brooks JD et al. |
 | Brooks JD, 2010 [56]d | Serum | QMSP (%) | 45/88 | 52/51.8 | 6.7 | 1.1 | >0.05 | |
 | Kim JH, 2010 [57] | Serum | QMSP (%) | 119/125 | 51/51 | 86.6 | 6.4 | <0.001 | |
 | Hoque M, 2006 [44] | Plasma | QMSP (%) | 47/38 | 44.9/37.3 | 26 | 8 | 0.03 | |
GSTP1 | Radpour R, 2011 [47] | Plasma | EpiTyper assay (mean) | 36/30 | 67/na | 0.52b | 0.39b | 0.003 | Two studies reported higher methylation level (Radpour R et al., 2011) or frequency (Hoque M et al., 2006) of GSTP1 in BC patients. Study by Brooks.J.D observed no significant differences. |
 | Brooks JD, 2010 [56]d | Serum | QMSP (%) | 50/99 | 52/51.8 | 4 | 7.1 | >0.05 | |
 | Hoque M, 2006 [44] | Plasma | QMSP (%) | 47/38 | 44.9/37.3 | 26 | 0 | 0.0008 | |
SFN | Zurita M, 2010 [54] | Serum | QMSP (%) | 77/34 | na/na | 0.002b | 0.1b | <0.001 | Both studies reported higher methlyation of SFN in BC patients. |
 | Martinez-Galan J, 2008 [51] | Serum | MSP (%) | 106/74 | 58/42 | 0.20b | 0.075b | 0.0047 | |
BRCA1 | Liu LM, 2015 [60] | Serum | Bisulfite sequencing PCR and MS-HRM (%) | 36a/30a | na/na | 10 | 1.7 | <0.05 | Both studies reported higher methlyation of BRCA1 in BC patients |
 | Radpour R, 2011 [47] | Plasma | EpiTyper assay | 36/30 | 67/na | 0.58b | 0.30b | <0.0001 | |
CST6 | Chimonidou M, 2013 [49] | Plasma | MSP (%) | 73/37 | na/na | 16.4 | 0 | Â | ChimonidouM et al. reported that CST6 promoter is highly methylated in cfDNA of breast cancer patients, but not in healthy individuals. Radpour R et al. observed higher methlytion level of CST6 in BC patients. |
 | Radpour R, 2011 [47] | Plasma | EpiTyper assay (mean) | 36/30 | 67/na | 0.62b | 0.42b | <0.002 | |
DAPK | Ahmed IA, 2010 [55] | Serum | MSP (%) | 26/12 | 35–73/35–73 | 88 | <10% | <0.05 | Higher frequency of methylated DAPK in patients was observed in both studies. |
 | Dulaimi E, 2004 [50] | Serum | MSP | 34/20 | 57.4/57.4 | 35 | 0 | <0.05c | |
TIMP3 | Zmetakova I, 2013 [42] | Plasma | Pyrosequencing (mean ± SD) | 34/50 | 41–90/20–78 | 3.97 ± 8.43 | 3.92 ± 4.54 | 0.697 | Zmetakova I et al. reported no significant difference in methylation of TIMP3 between patients and healthy controls. Radpour R et al. observed higher methylation level of TIMP3 in BC patients. |
 | Radpour R, 2011 [47] | Plasma | EpiTyper assay | 36/30 | 67/na | 0.60b | 0.50b | <0.0001 |