Plasma methylation markers for early colorectal cancer detection

Table 1 Demographic and clinical characteristics of the study cohort

Item	Control		Colorectal neoplasms
	Normal (n = 68)	Benign (n = 60)	Advanced adenoma (n = 5)	CRC (n = 117)
Age	56 (24-64)	60 (17-77)	67 (48-86)	64 (36-90)
Gender
Male	40	36	1	76
Female	28	24	4	41
Stage
I	-	-	-	19
II	-	-	-	38
III	-	-	-	36
IV	-	-	-	22
Unknown	-	-	-	2
Other gastrointestinal diseases
	Benign	Gastrointestinal stromal tumor	Esophageal tumor	Gastric tumor
Total (n)	1	1	2	19

Tumor stage was only applicable to patients with colorectal cancer tumor. “-” indicates not applicable. CRC: Colorectal cancer.

Table 2 Signal of markers detected in 51 white blood cell samples

Marker	Detected	Ratio
VIM	0	0%
VAV3-AS1	0	0%
ZEB2	2	3.9%
IKZF1	1	2%
KCNQ5	1	2%
NDRG4	21	41.2%
ITGA4	0	0%
C9orf50	0	0%
BCAN	35	68.6%
BMP3	40	78.4%
SDC2	11	21.6%
SEPT9-1	41	80.4%
SEPT9-2	2	3.9%
SFMBT2	0	0%
CHST11	0	0%
ZNF671	4	7.8%

Table 3 Discrimination of candidate markers for colorectal cancer in cancer and paracancerous tissues

Marker	Detected	Discrimination (%)	P value
CHST11	11	55%	0.049
C9orf50	18	90%	< 0.0001
SFMBT2	14	70%	< 0.0001
ZEB2	14	70%	< 0.0001
IKZF1	15	75%	0.0064
VAV3-AS1	10	50%	0.0589
ITGA4	15	75%	< 0.0001
SEPT9-2	6	30%	< 0.0001

Table 4 Relationship between the methylation panel and pathological characteristics of patients with colorectal neoplasms (advanced adenoma and colorectal cancer), n (%)

Variables	Panel positive (n = 98)	Panel negative (n = 24)	P value
Gender			0.8148
Male	61 (79.22)	16 (20.78)
Female	37 (82.22)	8 (17.78)
Age (years)			0.0285
< 50	10 (66.67)	5 (33.33)
50-60	23 (69.70)	10 (30.30)
> 60	65 (87.84)	9 (12.16)
Location			0.0721
Colon	39 (81.25)	9 (18.75)
Rectosigmoid transition	35 (89.74)	4 (10.26)
Rectum	24 (68.57)	11 (31.42)
Stage			0.0173
I	12 (63.16)	7 (36.84)
II	31 (81.58)	7 (18.42)
III-IV	53 (91.38)	5 (8.62)
Unknown	2 (100.00)	0 (0.00)
T stage			0.0028
T1-T2	13 (56.52)	10 (43.48)
T3	64 (88.89)	8 (11.11)
T4	17 (85.00)	3 (15.00)
Unknown	2 (100.00)	0 (0.00)
N stage			0.0382
N0	43 (74.14)	15 (25.86)
N1	35 (85.37)	6 (14.63)
N2	16 (100.00)	0 (0.00)
Unknown	2 (100.00)	0 (0.00)
M stage			0.0122
M0	73 (77.66)	21 (22.34)
M1	21 (100.00)	0 (0.00)
Unknown	2 (100.00)	0 (0.00)
Vascular invasion			0.2880
Absent	45 (77.59)	13 (22.41)
Present	44 (86.27)	7 (13.73)
Unknown	9 (69.23)	4 (30.77)
Nerve invasion			0.2136
Absent	27 (77.14)	8 (22.86)
Present	64 (84.21)	12 (15.79)
Unknown	7 (63.64)	4 (36.36)
Size			< 0.0001
< 5 cm	43 (66.15)	22 (33.85)
5 cm	47 (95.92)	2 (4.08)
Unknown	8 (100.00)	0 (0.00)

Advanced adenomas do not have a TNM stage; therefore, the TNM staging analyses (T, N, and M stages) were based on the 117 colorectal cancer cases only.