CpG island methylator phenotype in adenocarcinomas from the digestive tract: Methods, conclusions, and controversies

Table 5 Association between methylation and gene expression in tumor suppressor genes with significantly hypermethylated promoters in CpG island methylator phenotype + samples across four gastrointestinal adenocarcinoma types¹

		Differential methylation				Correlation with expression
Gene symbol	Promoter probes	Significant probes per cancer type				EAC		STAD		COAD		READ
		COAD	EAC	READ	STAD	cor	p-val	cor	p-val	cor	p-val	cor	p-val
TP73	24	18	3	2	23	-0.34	4.E-01	-0.24	1.E-01	-0.10	1.E+00	-0.20	1.E+00
MAL	8	6	5	2	7	-0.37	3.E-01	-0.46	2.E-07	-0.47	7.E-09	-0.45	3.E-02
C2orf40	8	5	3	1	7	-0.51	2.E-03	-0.57	5.E-13	-0.39	2.E-05	-0.24	6.E-01
TMEFF2	7	7	7	7	7	-0.54	2.E-03	-0.49	2.E-08	-0.41	2.E-03	-0.32	5.E-01
ERBB4	6	7	7	2	7	-0.26	5.E-01	-0.15	5.E-01	NA	1.E+00	-0.30	6.E-01
TWIST2	5	5	4	1	4	-0.26	3.E-01	-0.33	3.E-04	-0.38	2.E-06	-0.37	3.E-02
LRRC3B	13	9	7	1	12	-0.36	5.E-01	-0.38	2.E-04	-0.41	4.E-03	-0.11	1.E+00
HTRA3	10	6	3	1	6	0.02	1.E+00	-0.03	1.E+00	-0.10	1.E+00	-0.07	1.E+00
UNC5C	13	13	13	8	13	-0.38	7.E-02	-0.34	5.E-04	-0.43	4.E-08	-0.40	3.E-02
FAT4	13	13	9	2	13	-0.33	2.E-01	-0.44	4.E-07	-0.34	4.E-05	-0.28	4.E-01
IRX1	5	3	4	3	4	-0.37	2.E-01	-0.37	3.E-04	NA	1.E+00	NA	1.E+00
SCGB3A1	9	9	4	2	9	-0.27	4.E-01	-0.37	3.E-05	-0.22	3.E-01	-0.12	1.E+00
AKAP12	10	9	5	1	10	-0.19	1.E+00	-0.42	1.E-06	-0.42	7.E-08	-0.27	6.E-01
DFNA5	12	10	8	1	9	-0.75	0.E+00	-0.56	1.E-12	-0.36	1.E-05	-0.34	1.E-01
TFPI2	15	22	14	19	22	-0.49	3.E-03	-0.54	2.E-11	-0.38	4.E-06	-0.22	1.E+00
NRCAM	7	6	1	1	6	-0.52	3.E-04	-0.47	2.E-08	-0.19	8.E-02	-0.17	1.E+00
CNTNAP2	14	14	11	1	14	-0.14	1.E+00	-0.27	2.E-02	-0.14	1.E+00	-0.12	1.E+00
PAX6	12	12	5	3	11	-0.22	1.E+00	-0.18	6.E-01	-0.04	1.E+00	-0.32	3.E-01
WT1	12	12	12	3	12	-0.25	1.E+00	-0.04	1.E+00	-0.26	8.E-03	-0.23	1.E+00
PHOX2A	11	11	6	5	11	-0.26	1.E+00	-0.13	1.E+00	-0.38	3.E-03	-0.26	1.E+00
WIF1	8	5	5	3	7	-0.57	2.E-03	-0.32	5.E-03	-0.44	9.E-07	-0.56	2.E-04
SLC5A8	9	11	10	4	12	-0.26	1.E+00	-0.28	2.E-01	-0.17	1.E+00	-0.33	9.E-01
TBX5	17	11	7	1	16	-0.32	5.E-01	-0.09	1.E+00	0.03	1.E+00	-0.16	1.E+00
ATP8A2	8	5	4	2	5	-0.28	1.E-01	-0.37	2.E-05	-0.24	5.E-03	-0.24	3.E-01
ADAMTS18	8	7	5	3	7	-0.27	3.E-01	-0.36	6.E-05	-0.34	5.E-05	-0.30	2.E-01
GALR1	29	27	5	8	27	-0.17	1.E+00	-0.47	2.E-04	0.00	1.E+00	-0.14	1.E+00
RASSF2	5	6	4	3	6	-0.52	5.E-04	-0.31	1.E-03	-0.41	1.E-07	-0.40	2.E-02
CDH4	3	2	2	2	4	-0.17	6.E-01	-0.09	8.E-01	-0.16	3.E-01	-0.32	1.E-01

¹Promoter regions were designated as 2-kb regions encompassing 1.5 kb upstream and 0.5 kb downstream of the transcription start site. For each cancer type, probes were considered significant if the P-value after a one-sided Mann-Whitney U test with Bonferroni correction for multiple testing was < 0.05. The total number of probes considered across all four cancer types was 395814. COAD: Colon adenocarcinoma; EAC: Esophageal adenocarcinoma; READ: Rectal adenocarcinoma; STAD: Stomach adenocarcinoma.