Table 2.

Genes for which promoter methylation in serum or plasma has been shown to be associated with response to chemotherapy

Cancer type	Gene	n	Notes	Reference
Breast	Ten gene panel (AKR1B1, ARHGEF7, COL6A2, GPX7, TM6SF1, TMEFF2, HOXB4, RASGRF2, RASSF1A, HIST1H3)	29 patients (pre- and post-treatment sera)	Methylation decrease in patients having stable disease or therapeutic response	Fackler et al. (2014)
		No methylation decrease in patients with progressive disease
		13 patients (sera at three or more time points during therapy)	Ten out of 13 patients showed methylation levels reflective of tumor burden changes
	BRCA1	30 patients (serum)	Significantly lower baseline methylation in responders to neoadjuvant therapy	Sharma et al. (2012)
			Significantly higher baseline methylation in non-respondents to neoadjuvant therapy
	STRATIFIN	34 patients (serum)	Continuous decline in methylated STRATIFIN correspond to good prognosis	Zurita et al. (2010)
			Fluctuating STRATIFIN corresponded to poor prognosis
	RASSF1A	148 patients (serum)	Loss of methylation during treatment linked to good survival	Fiegl et al. (2005)
			Gain of methylation during treatment linked to poor survival
Prostate	GSTP1	35 patients (training set, plasma)	Baseline methylation a stronger predictor of overall survival than PSA change	Mahon et al. (2014)
		51 patients (validation set, plasma)	Undetectable methylation after one cycle of chemotherapy associated with PSA response
Lung	RARB2, RASSF1A	43 patients (pre-treatment, post-neoadjuvant therapy, post-surgery)	Methylation index decreased during neoadjuvant chemotherapy and following surgery	Ponomaryova et al. (2013)
		26 patients (∼2 weeks, and 3, 6, 9 months post-surgery, plasma and cell-surface-bound circDNA)	Five patients relapsed during follow up period and all five showed raise in methylation of one or both genes
		No patients without relapse showed increase in methylation in either gene
	CHFR	308 patients (plasma)	Methylation was strongly predictive of response to EGFR tyrosine kinase inhibitor	Salazar et al. (2011)
	STRATI-FIN	115 patients (serum)	Survival was significantly longer in the methylation positive group	Ramirez et al. (2005)
	SHOX2	36 patients (plasma)	Decrease in methylation 7–10 days after chemotherapy treatment identified responders	Schmidt et al. (2015)
	RASSF1A APC1	316 patients (plasma)	Methylation increase 24 h after chemotherapy associated with sensitivity	Wang et al. (2015)
Melanoma	RASSF1A	50 patients (serum)	Significantly less frequent methylation in pre-treatment of responders to biochemotherapy than non-responders	Mori et al. (2005)
Neuroblastoma	DCR2	Five patients (serum)	During follow-up methylation was close to 0 in patients in remission, and raised in patients who experienced recurrence	Yagyu et al. (2008)