Vastatin (the NC1 domain of human type VIII collagen a1 chain) is linked to stromal reactivity and elevated in serum from patients with colorectal cancer

Figures & data

Figure 1. Schematic illustration of the type VIII collagen a1-chain and vastatin with amino acid (aa) sequence. The proteases responsible for generating vastatin remains to be established. NC: non-collagenous domain.

Table 1. Subject characteristics.

Variable		Controls	CRC
Number of subjects		67	48
Age, median (range), years		48 (19–65)	71 (32–90)
Gender, n (% female)		18 (27%)	24 (50%)
BMI, median (range), kg/m^2		26.2 (21.7–31.7)	26.6 (17.6–37.9)
Tumor location, n (%)	Colon	-	41 (85%)
	Rectum	-	7 (15%)
Tumor stage, n (%)	Stage 1	-	7 (15%)
	Stage 2	-	25 (52%)
	Stage 3	-	9 (19%)
	Stage 4	-	4 (8%)
	N/A	-	3 (6%)
TNM classes, n (%)	T1N0M0	-	1 (2%)
	T2N0M0	-	6 (13%)
	T2N1M0	-	1 (2%)
	T3N0M0	-	23 (49%)
	T3N1M0	-	1 (2%)
	T3N0M1	-	2 (4%)
	T3N1M0	-	2 (4%)
	T3N1M1	-	1 (2%)
	T3N2M0	-	3 (6%)
	T3N2M1	-	1 (2%)
	T4N0M0	-	2 (4%)
	T4N1M0	-	2 (4%)
	N/A	-	3 (6%)
VI, n (%)	No	-	17 (36%)
	Yes	-	27 (56%)
	N/A	-	4 (8%)

CRC: colorectal cancer; BMI: body mass index; TNM: T: tumor, N: node, M: metastasis; VI: venous invasion

Figure 2. Serum vastatin in healthy controls and colorectal cancer (CRC) patients (a) and ROC curve analysis (b) for evaluating clinical accuracy of serum vastatin in CRC patients vs. the control group. In B), the area under the ROC curve was calculated to be AUC 0.865 (95%CI: 0.788–0.921), p < 0.0001. Optimal criterion value was 3 ng/ml with a sensitivity of 96% and specificity of 67%. A: Data presented as Tukey plots.

Figure 3. Serum vastatin according to gender (a) and age (b). In a subgroup analysis (c) of age-matched CRC patients (n = 13) and controls (n = 13) covering the age-span 30–65 years of age, significant difference in serum vastatin levels were maintained. CRC: colorectal cancer. A/C: Data presented as Tukey plots. B: Spearman correlation coefficient, r.

Table 2. Serum vastatin in CRC samples and relationship with clinico-pathological parameters.

Variable		Serum vastatin, ng/ml, median (range)	p-value
Tumor location	Colon	6.46 (1.88–17.43)	0.183
	Rectum	3.83 (3.02–37.41)
Tumor stage	Stage 1	5.77 (3.20–37.41)	0.885
	Stage 2	7.28 (1.88–17.39)
	Stage 3	5.66 (3.02–17.43)
	Stage 4	6.46 (3.83–11.37)
Tumor stage	Stage 1 + 2	6.41 (1.88–37.41)	0.702
	Stage 3 + 4	5.66 (3.02–17.43)
TNM class T	T1+ T2	6.28 (3.20–37.41)	0.919
	T3+ T4	6.03 (1.88–17.43)
TNM class N	N0	5.9 (1.88–37.41)	0.990
	N1 + 2	6.46 (3.02–17.43)
TNM class M	M0	6.03 (1.88–37.41)	0.803
	M1	6.46 (3.83–11.37)
VI	V0	6.79 (1.88–37.41)	0.489
	V1	5.38 (2.43–17.43)

CRC: colorectal cancer; TNM: T: tumor, N: node, M: metastasis; VI: venous invasion

Table 3. Stepwise multiple linear regression model for evaluating the independent association of clinicopathological parameters and stromal biomarkers with serum vastatin in patients with CRC.

Independent variables	Regression coefficient (bi)	Std. Error (sbi)	rpartial	p-value
C3M, ng/ml	0.252	0.122	0.310	0.046
Variables not included in the model: age, BMI, gender, TNM stage, tumour type, VI, VICM

CRC: colorectal cancer; BMI: body mass index; TNM: T: tumour, N: node, M: metastasis; VI: venous invasion; C3M: matrix metalloprotease degraded type III collagen (serum biomarker); VICM: matrix metalloprotease degraded and citrullinated vimentin (serum biomarker)

Figure 4. Impact of tumor resection (a) and adjuvant chemotherapy (b) on serum vastatin levels.