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

Table 5 Interaction between gene promoter region methylation and different cancer stages for 5-year overall survival 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	5 (15.2)	1.00	Referent	1.00	Referent	13	2 (15.4)	1.00	Referent	1.00	Referent
UnMe/advanced (3 and 4)2	29	8 (27.6)	2.24	0.73-6.86	4.84a	1.22-19.2	16	6 (37.5)	3.12	0.63-15.5	15.7a	1.98-124
Me/local (1 and 2)3	8	2 (25.0)	2.32	0.45-12.0	7.04	0.82-60.4	28	5 (17.9)	1.44	0.28-7.44	3.74	0.54-26.0
Me/advanced (3 and 4)4	21	5 (23.8)	1.85	0.53-6.41	5.96a	1.16-30.6	34	7 (20.6)	1.78	0.37-8.60	6.86	0.93-50.5
P value5				0.33		0.03				0.47		0.06
≥ 3 of genes6
UnMe/local (1 and 2)1	41	5 (12.2)	1.00	Referent	1.00	Referent	22	3 (13.6)	1.00	Referent	1.00	Referent
UnMe/advanced (3 and 4)2	44	11 (25.0)	2.57	0.89-7.40	5.28a	1.35-20.6	16	5 (31.3)	2.68	0.64-11.2	5.53	1.00-30.6
Me/local (1 and 2)3	17	4 (23.5)	2.69	0.72-10.0	4.46	0.93-21.5	36	6 (16.7)	1.59	0.40-6.35	2.04	0.38-11.1
Me/advanced (3 and 4)4	18	3 (16.7)	1.86	0.44-7.82	4.27	0.76-23.8	46	9 (19.6)	2.09	0.56-7.76	3.93	0.78-19.8
P value5				0.40		0.10				0.27		0.10

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.