Possible roles of insulin, IGF-1 and IGFBPs in initiation and progression of colorectal cancer

Table 1 Patient and disease characteristics

Characteristic	n
Gender
Male/female	335/280
Clinical Stage
T1/T2/T3	60/362/193
Type
Colon cancer/rectal cancer/colorectal cancer	193/410/12
Colon cancer
Pre/post-operation	53/140
Rectal cancer
Pre/post-operation	179/231
Health control
Male/female	368/282

Table 2 Comparisons of pre-operation and post-operation serum levels of biomarkers between colorectal cancer patients and healthy controls (x bar ± s)

Biomarker	Healthy controls (n = 650)	Pre-operation (n = 284)	Post-operation (n = 331)
Insulin (μIU/mL)	6.24 ± 4.70	9.82 ± 4.671	9.971 ± 6.011
IGF-1 (ng/mL)	136.73 ± 63.17	200.16 ± 44.071	209.84 ± 47.821
IGFBP-1 (ng/mL)	10.97 ± 3.58	12.23 ± 4.03	12.34 ± 4.31
IGFBP-3 (μg/mL)	9.24 ± 3.912	6.47 ± 3.053	7.05 ± 2.31
IGF-1/IGFBP-3	29.01 ± 10.002	39.02 ± 16.353	31.98 ± 13.49
Leptin (ng/mL)	9.01 ± 4.97	13.49 ± 8.351	13.79 ± 8.351

¹Compared to healthy controls, P < 0.001 and P < 0.05;

²Healthy controls compared to pre- and post- operation groups, which showed significant differences, P = 0.015 and P = 0.001;

³Pre-operation group compared to post-operation group, P = 0.02. IGF-1: Insulin-like growth factor-1; IFGBP-1: Insulin-like growth factor binding protein-1.

Table 3 Comparisons of serum levels of biomarkers between patients with and without post-surgical metastasis (x bar ± s)

Biomarker	With metastasis(n = 305)	Without metastasis(n = 66)	P value
Insulin (μIU/mL)	10.95 ± 7.57	10.05 ± 6.36	0.88
IGF-1 (ng/mL)	206.12 ± 22.65	200.64 ± 32.71	0.94
IGFBP-1 (ng/mL)	6.99 ± 2.94	6.91 ± 2.66	0.53
IGFBP-3 (μg/mL)	7.35 ± 3.85	7.01 ± 1.26	0.20
IGF-1/IGFBP-3	31.93 ± 11.91	30.99 ± 12.85	0.89
Leptin (ng/mL)	13.07 ± 4.86	13.43 ± 7.08	0.32

IGF-1: Insulin-like growth factor-1; IGFBP: Insulin-like growth factor binding protein.

Table 4 Comparisons of serum biomarker levels between colon cancer and rectal cancer patients (x bar ± s)

Biomarker	Colon cancer (n = 65)	Rectal cancer (n = 167)	P value
Insulin (μIU/mL)	8.04 ± 3.86	10.01 ± 4.86	0.095
Leptin (ng/mL)	12.80 ± 5.81	13.76 ± 5.69	0.144
IGF-1 (ng/mL)	181.01 ± 38.01	207.39 ± 39.62	0.041
IGFBP-1 (ng/mL)	9.82 ± 1.81	11.99 ± 4.28	0.022
IGFBP-3 (μg/mL)	6.04 ± 2.19	6.31 ± 3.66	0.73
IGF-1/IGFBP-3	30.81 ± 9.64	39.57 ± 15.24	0.033

IGF-1: Insulin-like growth factor-1; IGFBP: Insulin-like growth factor binding protein.

Table 5 Comparisons of body mass index and waist-to-hip ratio between colorectal cancer patients and healthy controls (x bar ± s)

Group	Body mass index	WHR
Colon cancer	23.99 ± 3.95	0.99 ± 0.06112
Rectal cancer	24.01 ± 3.62	0.90 ± 0.0171
Healthy controls	23.26 ± 2.96	0.81 ± 0.037

¹Comparison of WHR between colorectal cancer patients and healthy controls, P = 0.003 and P =0.035;

²Comparison of WHR between colon cancer patients and rectal cancer patients, P = 0.046. WHR: Waist-to-hip ratio.

Table 6 Associations of waist-to-hip ratio and body mass index of colon cancer patients with the levels of leptin, insulin, insulin-like growth factor, insulin-like growth factor binding protein-1, insulin-like growth factor binding protein-3 and insulin-like growth factor-1/insulin-like growth factor binding protein-3 ratio

Biomarker	WHR Pearson correlation	BMI Pearson correlation	P value
Insulin	0.519	0.485	< 0.001 0.002
Leptin	0.396	0.448	< 0.001 < 0.001
IGF-1	0.394	0.172	> 0.05 > 0.05
IFGBP-1	-0.259	0.082	> 0.05 > 0.05
IGFBP -3	-0.443	-0.342	0.005 0.018
IGF-1/IGFBP3	0.501	0.296	0.045 0.050

IGF-1: Insulin-like growth factor-1; IFGBP-1: Insulin-like growth factor binding protein-1; WHR: Waist-to-hip ratio; BMI: Body mass index.

Table 7 Analysis of serum insulin, insulin-like growth factor-1, insulin-like growth factor binding proteins, and insulin-like growth factor-1/insulin-like growth factor binding protein-3 ratio

Stage	n	Insulin(mU/L)	IGF-1(μg/L)	IGFBP-1(μg/L)	IGFBP-3(μg/L)	IGF-1/IGFBP-3
T1	60
Pre-operation		7.85 ± 4.87	153.52 ± 32.65	8.25 ± 1.24	8.25 ± 3.25	18.61 ± 10.01
Post-operation		7.68 ± 5.07	151.46 ± 39.19	7.91 ± 4.66	9.65 ± 4.06	15.70 ± 9.65
P value		P > 0.05	P > 0.05	P > 0.05	P < 0.05	P < 0.05
T2	362
Pre-operation		10.51 ± 6.03	200.37 ± 52.45	11.95 ± 2.69	5.95 ± 3.26	33.68 ± 16.08
Post-operation		8.78 ± 8.07	148.58 ± 45.63	9.06 ± 4.31	8.84 ± 4.06	16.81 ± 11.01
P value		P < 0.05	P < 0.05	P < 0.05	P < 0.05	P < 0.05
T3	193
Pre-operation		11.25 ± 6.57	209.69 ± 48.11	12.25 ± 3.01	5.75 ± 3.86	36.47 ± 12.46
Post-operation		8.83 ± 8.07	150.78 ± 35.21	9.85 ± 3.66	8.63 ± 3.33	17.48 ± 10.57
P value		P < 0.05	P < 0.05	P < 0.05	P < 0.05	P < 0.05

IGF-1: Insulin-like growth factor-1; IFGBP-1: Insulin-like growth factor binding protein-1.