Novel methylation gene panel in adjacent normal tissues predicts poor prognosis of colorectal cancer in Taiwan

Table 4 Interaction between gene promoter region methylation and different cancer stages for 5-year time to progression of colorectal cancer patients, n (%)

	Normal tissues						Tumor tissues
	No. of subjects	No. of cases	Crude		Adjusted		No. of subjects	No. of cases	Crude		Adjusted
			HR	95%CI	HR	95%CI			HR	95%CI	HR	95%CI
OAF
UnMe/local (1 and 2)1	33	3 (9.1)	1.00	Referent	1.00	Referent	13	0 (0.0)	1.00	Referent	1.00	Referent
UnMe/advanced (3 and 4)2	29	20 (69.0)	14.7a	3.38-63.6	16.6a	3.69-74.6	16	12 (75.0)	N/A	N/A	N/A	N/A
Me/local (1 and 2)3	8	0 (0.0)	N/A	N/A	N/A	N/A	28	3 (10.7)	N/A	N/A	N/A	N/A
Me/advanced (3 and 4)4	21	18 (85.7)	19.0a	4.30-84.6	20.3a	4.12-100	34	26 (76.5)	N/A	N/A	N/A	N/A
P value1				< 0.01		< 0.01
≥ 3 of genes6
UnMe/local (1 and 2)1	41	2 (4.88)	1.00	Referent	1.00	Referent	22	2 (9.09)	1.00	Referent	1.00	Referent
UnMe/advanced (3 and 4)2	44	25 (56.8)	13.3a	3.10-57.0	11.9a	2.72-51.8	16	7 (43.8)	7.17	0.80-64.2	6.56	0.72-59.4
Me/local (1 and 2)3	17	1 (5.88)	N/A	N/A	N/A	N/A	36	1 (2.78)	0.63	0.04-9.99	0.59	0.04-9.62
Me/advanced (3 and 4)4	18	17 (94.4)	33.4a	7.49-149	28.8a	6.24-133	46	35 (76.1)	23.1a	3.14-170	20.8a	2.75-157
P value5				< 0.01		< 0.01				< 0.01		< 0.01

¹DNA promoter region unmethylation with cancer stage 1 or 2;

²DNA promoter region unmethylation with cancer stage 3 or 4;

³DNA promoter region methylation with cancer stage 1 or 2;

⁴Me/advanced (3 and 4): DNA promoter region methylation with cancer stage 3 or 4;

⁵P for the joint effect interaction;

⁶Including CDKN2A, hMLH1, MGMT, CSF2, DIS3L2, and OAF.

^aP < 0.05. Adjusted for gender, age at surgery (continuous), adjuvant chemotherapy, histological grade, and tumor location. CI: Confidence interval; HR: Hazard ratio; OAF: The out at first homolog gene; N/A: Not applicable.