Table 2.

Prognostic and predictive DNA methylation biomarkers for gastric cancer.

Gene /panel	Material	Cancer samples	Stage	Effect of methylation	Survival/Response	Method	Ref
APC	Serum	79	I-IIIAB	Poor OS	^*HR = 4.6, P = .046	MSP	[201]
APC, CDH1	Serum	58	I-IV	Poor survival	P = .0006	qMSP	[202]
ASC/TMS1	Tissue	200	T1-T4/N0-N3	Poor OS	^*HR = 0.536, P = .001	MSP	[203]
BCL6B	Tissue	208 (cohort 1)	I-IV	Poor OS	^*RR = 2.14, P = .001	COBRA, BGS	[75]
		101 (cohort 2)			^*RR = 1.85, P = .02
BNIP	Tissue	80	IV or recurrence	Poor OS	P = .031	MSP	[76]
BNIP, DAPK	Tissue	80	IV or recurrence	Lower response to 5-FU	P = .003 (RECIST)	MSP	[76]
BNIP, DAPK	Tissue	80	IV or recurrence	Poor OS	P = .001	MSP	[76]
				Poor PFS	P = .002
CACNA2D3	Tissue	53	Advanced^a	Poor survival	^*OR = 4.38, P = .002	MSP, BGS	[204]
CDH1	PPW	92	I-IV	Poor DFS	RR = 333, P < .001	qMSP	[82]
CDH1	Serum	97	I-IV	Poor OS	P < .05	MSP	[83]
CDH1	Tissue	73	II-III	Poor DFS	^*RR = 2.28, P < .001	MSP	[84]
				Poor OS	^*RR = 1.94, P = .004
CDKN2A	Tissue	119	I-IV	Poor survival	P < .0001	MSP	[87]
CDKN2A	Tissue	38 (chemotherapy)	I-IV	Improved DFS	^*RR = 0.093, P = .043	MSP	[88]
CDO1	Peritoneal washes	102	I-IV	Poor OS	P = .0004	qMSP	[205]
	Peritoneal washes			Poor RFS	P = .005
CHFR	Tissue	12	Advanced^a or recurrence	Improved response to TXL or TXT	86% PR or NC (CHFR+), 20% PR or NC (CHFR−)	MSP	[206]
CIMP	Tissue	68	I-IV	Improved OS	P = .069	COBRA	[81]
CIMP/MLH1	Tissue	68	I-IV	Improved OS	^*P = .031	COBRA	[81]
DAPK	Tissue	81	I-IV	Poor OS	P = .045	MSP	[77]
DAPK	Tissue	80	IV or recurrence	Lower response to 5-FU	P = .012 (RECIST)	MSP	[76]
DAPK	Tissue	80	IV or recurrence	Poor PFS	P = .007	MSP	[76]
DAPK and TMS1	Tissue	81	I-IV	Poor OS	P < .001	MSP	[77]
				Poor RFS	P < .0001
DAPK and TMS1	Tissue	43 (5-FU)	IV or recurrence	Poor OS	P = .083	MSP	[77]
				Poor TTR	P = .008
DAPK1	Tissue	141	I-IV	Poor OS	P = .04	qMSP	[207]
					^*OR = 1.13, P > .05
DKK2	Tissue	92	I-IV		^*HR = 2.05, P = .041	Pyrosequencing	[208]
DLEC1	Tissue	148	I-IV	Poor RFS	^*HR = 2.43, P = .025	qMSP	[209]
FLNc	Tissue	119	I-IV	Poor survival	P = .03	MSP	[87]
GFRA3	Tissue	24	I-IV	Poor OS	^*P = .01	Illumina HM27K	[210]
IGF2	Leukocytes	299	I-IV	Improved OS	^*HR = 0.42, P = .001	qMSP	[80]
MGMT	Tissue	79	I-IV	Poor DFS	P < .02	MSP	[211]
MGMT	Tissue	119	I-IV	Poor survival	P = .02	MSP	[87]
MINT2	Serum	92	I-IV	Poor DFS	^*RR = 4.11, P < .05	qMSP	[212]
	PPLF				^*RR = 3.26, P < .05
MLH1	Tissue	68	I-IV	Improved OS	P = .026	COBRA	[81]
NDRG4	Tissue	110	I-IV	Poor OS	^*HR = 1.887, P = .020	qMSP, pyrosequencing	[78]
PAX5	Tissue	460	T1-T4/N0-N3	Poor OS	^*HR = 1.39, P = .005	BGS	[213]
PAX5	Tissue	187	I-IV	Poor OS	^*RR = 2.10, P = .01	MSP, BGS	[214]
PAX6	Tissue	141	I-IV	Poor OS	P < .001	qMSP	[207]
					^*OR = 1.51, P > .05
PCDH10	Tissue	104	I-IV	Poor OS	^*RR = 1.73, P = .039	COBRA	[61]
PCDH10	Tissue	471	T1-T4/N0-N3	Poor OS	^*HR = 1.41, P = .011	BGS	[215]
RARb	Tissue	141	I-IV	Poor OS	P < .001	qMSP	[207]
					^*OR = 2.04, P > .05
RASSF10	Serum	82	I-IV	Poor OS	^*OR = 13.96, P < .001	BGS	[216]
				Poor DFS	^*OR = 13.11, P < .001
RASSF1A	Tissue	141	I-IV	Poor OS	P = .004	qMSP	[207]
					^*OR = 1.72, P > .05
RASSF2A	Tissue	119	I-IV	Poor survival	P = .01	MSP	[87]
RKIP	Tissue	76	I-IV	Poor survival	^*OR = 0.22, P = .042	MSP	[217]
RNF180	Plasma	32	I-IV	Poor CSS	^*RR = 2.13, P = .02	qMSP	[68]
RPRM	Tissue	49 (5-FU + cisplatin)	IV or recurrence	Poor DSS	P = .05	qMSP	[86]
RPRM	Tissue	68	Advanced^a	Poor DSS	^*HR = 2.148, P = .026	qMSP	[86]
SPARC	Tissue	185	I-IV	Poor OS	^*RR = 2.75, P < .001	MSP	[218]
TIMP3	PPW	92	I-IV	Poor DFS	^*HR = 1.72, P < .001	qMSP	[219]
TIMP3	Serum	92	I-IV	Poor DFS	^*HR = 1.55, P = .03	qMSP	[219]
XAF1	Serum	202	I-IV	Poor DFS	^*HR = 5.71, P < .001	qMSP	[85]

Abbreviations: BGS, bisulfite genomic sequencing; COBRA, combined bisulfite restriction analysis; DSS, disease specific survival; HR, hazard ratio; MSP, methylation specific PCR; NC, no change; OR, odds ratio; OS, overall survival; PPLF, preoperative peritoneal lavage fluid; PPW, preoperative peritoneal washes; PR; partial response; qMSP, quantitative methylation specific PCR; RECIST, response evaluation criteria in solid tumors; RFS, relapse/recurrence free survival; RR, relative risk; TTP, time to progression; TXT, Taxotere; TXL, Taxol.

Invading muscuaris propria.

Multivariate.