Clinical significance of differential plasma proteins levels in the diagnosis of epithelial ovarian cancer

Table 1 Characteristics of the included control, benign, and ovarian cancer patients (malignant cases), n (%)

Variables		Control (n = 30)	Benign (n = 10)	Malignant (n = 50)
Age (years)	mean ± SD	48.4 ± 8	50.7 ± 8.3	52.3 ± 14.5
	Median (range)	49 (23-54)	48.5 (41-66)	50.5 (25-86)
Family history	Positive		1(10.0)	6 (12.0)
	Negative		9 (90.0)	44 (88.0)
Metastasis	Positive			34 (68.0)
	Negative			16 (32.0)
Site of metastasis	Omentum/peritoneum			29 (58.0)
	Ileum			1 (2.0)
	Ileum and rectum			1 (2.0)
	Pancreas			1 (2.0)
	Liver			1 (2.0)
	Lymph nodes			1 (2.0)
Tumor markers	Carcinoembryonic antigen			65.6 (3.34-116.2)
	CA19-9			475.95 (41.3-7174)
	CA15-3			47.25 (27.39-353.3)

CA: Cancer antigen.

Table 2 Plasma protein levels in different study groups

	Control (n = 30)	Benign (n = 10)	Malignant (n = 50)	P value
Cancer antigen 125 (U/mL)	12.2 (3.1-25.9)a	28.6 (3.5-1217)b	232 (5.5-3649)c	< 0.001
Human epididymis protein 4 (pmol/L)	41.6 (3.8-83.8)a	93.4 (37-800)b	283 (37-5908)b	< 0.001
Insulin-like growth factors-binding proteins 2 (pg/mL)	273 (117-353)a	2641 (1114-3773)b	2669 (146-5785)b	< 0.001
Thrombospondin 1 protein (pg/mL)	2899 (95-8500)	1702 (560-3540)	1803 (92-8500)	0.051
Secreted phosphoprotein 1 (ng/mL)	4.2 (1.9-6.3)a	3.98 (0.85-11.5)a	40.4 (11-76.5)b	< 0.001
D-dimer (ng/mL)	0.1 (0-0.5)a	832 (262-3429)b	744 (50-1000)b	< 0.001

^aP < 0.05.

^bP < 0.01.

^cP < 0.001.

Analysis was done using Kruskal-Walli’s test with post hoc pairwise Mann Whiteny test.

Table 3 Diagnostic accuracy of the assessed markers for the epithelial ovarian cancer patients

Test variables	Area under the receiver operating characteristic curve	Cutoff value	Sensitivity	Specificity	P value
CA125	0.943	41.1	90%	100%	< 0.001
HE4	0.936	66.4	82%	93.3%	< 0.001
Insulin-like growth factors-binding proteins 2	0.981	553.1	98%	100%	< 0.001
TSP1	0.653	2460	70%	66.7%	0.046
SPP1	0.908	8.64	86.7%	100%	< 0.001
TSP1 + SPP1	0.968	-	93.3%	100%	< 0.001
CA125 + SPP1	0.968	-	93.3%	100%	< 0.001
CA125 + HE4	0.962	-	91.7%	93.3%	< 0.001
CA125 + TSP1	0.949	-	95%	83.3%	< 0.001

CA125: Cancer antigen 125; HE4: Human epididymis protein 4; SPP1: Secreted phosphoprotein 1; TSP1: Thrombospondin 1 protein.

Table 4 Regression analysis for the diagnosis of epithelial ovarian cancer patients

	Odds ratio	95%CI for Exp(B)		P value
		Lower	Upper
Age	1.103	1.049	1.159	0.001
Family history	0	0.00	0.00	0.999
Menopausal status	0	0.00	0.00	0.999
Cancer antigen 125	1.072	1.025	1.122	0.002
Human epididymis protein 4	1.069	1.030	1.111	0.001
Insulin-like growth factors-binding proteins 2	1.009	1.000	1.017	0.044
Thrombospondin 1 protein	1.000	1.000	1.000	0.080
Secreted phosphoprotein 1	1.375	1.092	1.732	0.007
D-dimer	1.674	0.000	3611171.830	0.945

Table 5 Correlation among the tested variables in epithelial ovarian cancer patients

		HE4	IGFBP2	TSP1	SPP1	CA19-9	CA15-3	D-dimer
CA125	r value	0.365	0.131	0.001	0.183	-0.071	-0.446	0.046
	P value	0.004	0.318	0.995	0.161	0.879	0.268	0.791
HE4	r value		-0.018	0.101	0.255	-0.536	0.759	0.220
	P value		0.891	0.444	0.050	0.215	0.029	0.204
IGFBP2	r value			0.306	0.031	-0.643	0.470	0.376
	P value			0.018	0.815	0.119	0.240	0.026
TSP1	r value				-0.058	-0.643	0.349	-0.298
	P value				0.707	0.119	0.396	0.082
SPP1	r value					0.107	0.325	-0.009
	P value					0.819	0.432	0.959

r: Spearman's rho. CA: Cancer antigen; HE4: Human epididymis protein 4; IGFBP2: Insulin-like growth factors-binding proteins 2; SPP1: Secreted phosphoprotein 1; TSP1: Thrombospondin 1 protein.