Early detection of colorectal cancer based on circular DNA and common clinical detection indicators

Table 1 General clinical characteristics of study subjects

Clinical features	Model building		Model validation
	CRC (n = 101)	CRP (n = 59)	CRC (n = 62)	CRP (n = 30)
Age
Average	58	56	57	57
Range	29-81	31-76	33-74	35-69
Sex
Male	60	34	37	19
Female	41	25	25	11
Location
Ascending colon	21		17
Descending colon	15		12
Transverse colon	3		4
Sigmoid colon	59		28
Rectal	3		1
Differentiation
Well	21		15
Moderate	57		33
Poorly	23		14
TNM stage
T1	11		11
T2	27		21
T3	44		7
T4	19		23

CRP: Colorectal polyps; CRC: Colorectal cancer; TNM: Tumor node metastasis.

Table 2 Comparison of 51 common clinical indicators between colon polyp group and colorectal cancer group

Index	CRP (n = 59)	CRC (n = 101)	F value	Sig	P value
CEA	1.86 (1.17, 2.43)	3.9 (1.67, 13.87)	11.39	< 0.01	< 0.01
AFP	2.58 (1.87, 3.59)	2.41 (1.75, 3.36)	0.02	0.90	0.41
CA125	9.78 (6.77, 13.55)	11.63 (7.98, 19.9)	4.80	0.03	0.04
CA199	8.57 (5.44, 14.38)	13.43 (7.22, 26.48)	3.62	0.06	0.22
CA153	9.5 (7.08, 13.09)	9.25 (6.6, 13)	1.53	0.22	0.49
CA724	1.63 (1.16, 4.39)	2.55 (1.36, 7.33)	5.54	0.02	0.07
CY211	1.82 (1.4, 2.89)	2.3 (1.63, 3.58)	9.29	< 0.01	< 0.01
Ferr	150.9 (85.62, 269.5)	72.12 (17.02, 161.5)	0.11	0.74	0.01
NSE	8.06 (6.52, 9.16)	10 (7.71, 12.63)	4.58	0.03	< 0.01
SCC	1.1 (0.7, 1.5)	0.8 (0.6, 1.2)	2.96	0.09	0.19
PG I/II	4.576 (2.835, 5.914)	5.12 (3.7, 6.53)	0.10	0.76	0.08
PG II	15.9 (9, 28.3)	14.6 (9.7, 24.2)	1.08	0.30	0.64
PG I	75.5 (38.5, 101.3)	71.7 (51.45, 96.3)	0.49	0.49	0.82
ALT	16.8 (12.1, 25)	12.7 (9.3, 17.75)	0.59	0.44	0.03
AST	17.1 (14.1, 20.6)	16.6 (12.25, 19.3)	0.87	0.35	0.43
TP	68.3 (64.1, 71.9)	67.3 (63.15, 70.65)	0.03	0.86	0.29
ALB	41.8 (39.6, 44.4)	39.5 (36.95, 41.45)	0.63	0.43	0.07
TB	12.5 (10, 16.4)	9.7 (7.4, 12.8)	0.75	0.39	< 0.01
DB	4.1 (3.2, 5.2)	3.6 (2.3, 4.2)	0.05	0.82	0.01
TBA	4.2 (2.5, 7.2)	3.5 (2.2, 5.7)	2.15	0.14	0.11
ALP	61.4 (54.8, 73.6)	67 (56.4, 80.05)	2.38	0.13	0.59
GGT	23.6 (13.5, 37.6)	22.3 (14.75, 33.95)	0.01	0.95	0.98
GLu	5.02 (4.79, 5.51)	5.12 (4.74, 5.81)	0.00	0.97	0.97
UN	5.49 (4.64, 6.08)	5.23 (4.08, 6.29)	5.94	0.02	0.43
Cr	70.2 (61.6, 78.6)	65.2 (56.35, 75.6)	0.22	0.64	0.06
UA	312.3 (257.9, 386.9)	292.8 (224, 339.4)	0.19	0.67	0.06
CHO	4.5 (4.04, 5.27)	4.36 (3.88, 5.09)	2.31	0.13	0.02
TG	1.43 (1.01, 2.01)	1.25 (0.93, 1.62)	7.94	0.01	0.45
CK	69.8 (55.5, 118.9)	54.4 (35.2, 71.05)	15.60	< 0.01	0.04
LDH	137 (122.2, 153.3)	148.4 (129.75, 177.75)	4.13	0.04	< 0.01
CKMB	6.6 (4, 9.8)	6.14 (4.05, 9.6)	1.81	0.18	0.02
Ca	2.26 (2.19, 2.31)	2.21 (2.14, 2.27)	0.10	0.75	0.47
P	1.27 (1.14, 1.39)	1.25 (1.07, 1.38)	0.01	0.93	0.01
Mg	0.93 (0.85, 1.01)	0.91 (0.84, 0.97)	0.01	0.94	0.29
K	4.03 (3.78, 4.18)	4.09 (3.87, 4.33)	4.98	0.03	0.53
Na	143.8 (141.6, 145.4)	143.1 (141.45, 144.7)	0.17	0.68	0.12
Cl	105.6 (103.4, 107.2)	105.3 (103.5, 107.4)	2.08	0.15	0.04
CO2	22.6 (20.7, 26.1)	24.9 (22.9, 26.65)	2.31	0.13	0.40
LPa	7.83 (3.01, 12.74)	15.65 (7.82, 31.65)	13.29	< 0.01	0.01
HDL	1.27 (1.03, 1.41)	1.02 (0.89, 1.23)	0.10	0.76	< 0.01
LDL	2.63 (2.26, 3.28)	2.54 (2.07, 3.27)	1.33	0.25	< 0.01
ApoA1	1.39 (1.17, 1.54)	1.13 (1.01, 1.34)	0.66	0.42	0.55
ApoB	0.83 (0.72, 1.02)	0.83 (0.72, 1.01)	0.09	0.76	0.62
CYS	1.07 (0.95, 1.16)	0.97 (0.84, 1.08)	0.34	0.56	0.70
SA	59.3 (55, 66.5)	67.1 (60.8, 82.4)	13.50	< 0.01	0.04
HCY	15.19 (11.54, 19.68)	13.92 (11.18, 17.42)	4.71	0.03	< 0.01
CRP	0.7 (0.4, 1.5)	3.9 (1, 10.55)	30.41	< 0.01	0.11
AMY	59.5 (50, 73.7)	51.8 (38.95, 64.7)	1.18	0.28	< 0.01
LPS	33.1 (25.1, 42.7)	32.9 (22.25, 44.25)	2.87	0.09	0.06
SOD	136.1 (125, 147)	136.5 (115.8, 156.9)	4.82	0.03	0.35
IMA	63.8 (60.1, 66.3)	62.1 (59.45, 67.5)	0.11	0.74	< 0.01
NDUFB7	1.34 (0.94, 2.42)	2.10 (1.29, 3.08)	2.666	0.105	0.155
CAMK1D	34.21 (17.82, 103.44)	70.39 (35.26, 155.57)	3.045	0.083	0.030
PIK3CD	105.90 (36.69, 308.35)	333.22 (259.40, 417.90)	3.700	0.056	0.001
PSEN2	6.46 (4.44, 11.03)	8.69 (6.00, 11.67)	0.144	0.705	0.154

CRP: Colorectal polyps; CRC: Colorectal cancer; CEA: Carcinoembryonic antigen; AFP: Alpha fetoprotein; CA125: Carbohydrate antigen 125; NSE: Neuron-specific enolase; SCC: Squamous cell carcinoma; PG: Pepsinogen; ALT : Alanine aminotransferase; AST: Aspartate aminotransferase; TP: Total protein; ALB: Albumin; TB: Total bilirubin; DB: Direct bilirubin; TBA: Total bile acid; ALP: Alkaline phosphatase; GGT: γ-glutamyl transfer enzyme; Glu: Glucose; UN: Urea nitrogen; Cr: Creatinine; UA: Uric acid; CHO: Cholesterol; TG: Triglyceride esters; CK: Creatine kinase; LDH: Lactate dehydrogenase; CKMB: Creatine kinase isoenzyme; Ca: Calcium; P: Phosphorus; Mg: Magnesium; K: Potassium; Na: Sodium; Cl: Chlorine; CO₂: Carbon dioxide; LPa: Lipoprotein a; HDL: High-density lipoprotein; LDL: Low-density lipoprotein; ApoA1: Apolipoprotein A1; CYS: Cysteine; SA: sialic acid; HCY: Homocysteine; CRP: C-reactive protein; AMY: Amylase; LPS: Lipase; SOD: Superoxide dismutase; IMA: Ischemia-modified albumin.

Table 3 Evaluation of the diagnostic value of 26 commonly used clinical indicators with statistical differences (colon polyp group vs colorectal cancer group)

Indicator	AUC	SE	P value	95% CI
				Lower	Upper
IMA	0.787	0.036	< 0.001	0.716	0.859
CEA	0.734	0.038	< 0.001	0.658	0.809
SA	0.728	0.039	< 0.001	0.651	0.804
LPa	0.715	0.042	< 0.001	0.633	0.797
CK	0.702	0.042	< 0.001	0.619	0.784
TB	0.672	0.044	< 0.001	0.585	0.758
HDL	0.670	0.044	< 0.001	0.583	0.758
NSE	0.668	0.044	< 0.001	0.580	0.755
ALT	0.667	0.044	< 0.001	0.580	0.754
Ferr	0.663	0.045	0.001	0.575	0.751
DB	0.646	0.044	0.002	0.559	0.733
CA125	0.642	0.044	0.003	0.557	0.728
LDH	0.621	0.045	0.011	0.534	0.709
AMY	0.611	0.045	0.019	0.522	0.700
CY211	0.602	0.046	0.032	0.513	0.691
CA724	0.583	0.046	0.081	0.492	0.673
HCY	0.570	0.048	0.138	0.476	0.664
CHO	0.556	0.046	0.240	0.465	0.646
P	0.543	0.047	0.361	0.451	0.636
LDL	0.536	0.046	0.453	0.445	0.626
Cl	0.525	0.047	0.603	0.432	0.618
CKMB	0.516	0.047	0.736	0.424	0.608
CAMK1D	0.652	0.046	0.001	0.561	0.742
PIK3CD	0.753	0.047	< 0.001	0.660	0.845

AUC: Area under the curve; CEA: Carcinoembryonic antigen; AFP: Alpha fetoprotein; CA125: Carbohydrate antigen 125; NSE: Neuron-specific enolase; PG: Pepsinogen; ALT : Alanine aminotransferase; AST: Aspartate aminotransferase; TP: Total protein; ALB: Albumin; TB: Total bilirubin; DB: Direct bilirubin; TBA: Total bile acid; ALP: Alkaline phosphatase; GGT: γ-glutamyl transfer enzyme; CK: Creatine kinase; LDH: Lactate dehydrogenase; CKMB: Creatine kinase isoenzyme; Ca: Calcium; P: Phosphorus; Cl: Chlorine; LPa: Lipoprotein a; HDL: High-density lipoprotein; LDL: Low-density lipoprotein; ApoA1: Apolipoprotein A1; CYS: Cysteine; SA: sialic acid; HCY: Homocysteine; CRP: C-reactive protein; AMY: Amylase; IMA: Ischemia-modified albumin.

Table 4 Univariate Logistic Regression Analysis between the colon polyp group and the colorectal cancer group with statistically significant between-group and receiver operating characteristic indicators

Indicator	B	SE	Wals	P value	Exp (B)	95% CI
						Lower	Upper
CEA	0.335	0.138	5.864	0.015	1.398	1.066	1.834
IMA	-0.138	0.048	8.352	0.004	0.871	0.793	0.956
SA	0.078	0.034	5.347	0.021	1.081	1.012	1.155
LPa	0.085	0.027	9.844	0.002	1.089	1.032	1.148
CK	-0.004	0.008	0.207	0.649	0.996	0.980	1.013
TB	-0.065	0.054	1.463	0.226	0.937	0.843	1.041
HDL	-0.949	0.822	1.331	0.249	0.387	0.077	1.941
NSE	0.160	0.084	3.656	0.056	1.174	0.996	1.383
CHO	-0.004	0.017	0.053	0.817	0.996	0.964	1.029
P	0.886	1.104	0.644	0.422	2.426	0.279	21.139
LDL	0-.585	0.368	2.534	0.111	0.557	0.271	1.145
Cl	0.112	0.086	1.682	0.195	1.119	0.944	1.325
CKMB	-0.025	0.057	0.202	0.653	0.975	0.872	1.089
CAMK1D	0.003	0.003	1.189	0.275	1.003	0.998	1.009
PIK3CD	0.003	0.001	4.429	0.035	1.003	1.000	1.005

CEA: Carcinoembryonic antigen; TB: Total bilirubin; CKMB: Creatine kinase isoenzyme; P: Phosphorus; Cl: Chlorine; LPa: Lipoprotein a; HDL: High-density lipoprotein; LDL: Low-density lipoprotein; SA: sialic acid; IMA: Ischemia-modified albumin.

Table 5 Multivariate Logistic Regreesion Analysis Exp (B) Indicators with Statistical Differences (Colon polyp group vs colorectal group)

Indicator	B	SE	Wals	P value	Exp (B)	95% CI
						Lower	Upper
CEA	0.326	0.109	8.904	0.003	1.385	1.118	1.716
IMA	-0.136	0.035	14.765	< 0.001	0.873	0.815	0.936
SA	0.092	0.027	11.601	0.001	1.097	1.040	1.156
PIK3CD	0.002	0.001	5.852	0.016	1.002	1.000	1.004
LPa	0.064	0.022	8.888	0.003	1.066	1.022	1.112

CEA: Carcinoembryonic antigen; IMA: Ischemia-modified albumin; LPa: Lipoprotein a; SA: sialic acid.

Table 6 Multi-parameter combined auxiliary diagnosis model building

Observed	Predicted
	CRP	CRC	Correct percentage
Binary logistic regression analysis building
CRP	45	14	76.30%
CRC	15	86	85.10%
Total percentage			81.90%
Discriminant analysis building
CRP	51	8	86.40%
CRC	31	70	69.30%
Total percentage			75.60%
Classification tree building
CRP	54	5	91.50%
CRC	42	59	58.40%
Total percentage			70.60%
Neural network building
CRP	31	8	79.50%
CRC	2	68	97.10%
Total percentage			90.80%
Neural network validation
CRP	18	2	90.00%
CRC	4	27	87.10%
Total percentage			88.20%

CRP: Colorectal polyps; CRC: Colorectal cancer.