Thioredoxin-1 and MMP-9 as biomarkers in breast cancer metastasis in Egyptian female patients

Figures & data

Table 1 Clinical characteristics of metastatic and non-metastatic breast cancer patients.

Items	Non metastatic breast cancer patients (n = 37)		Metastatic breast cancer patients (n = 38)		Test of sig. p-value
	No	%	No	%
Staging^a
Stage I	12	32.4	0	0	X^2 = 75 p < .001
Stage II	12	32.4	0	0
Stage III	13	35.2	0	0
Stage IV	0	0	38	100
Grading
G1	10	27.0	0	0	X^2 = 16.014 p < .001
G2	21	56.8	20	52.6
G3	6	16.2	18	47.4
Tumor size
T1	13	35.1	0	0	X^2 = 40.45 p < .001
T2	11	29.7	1	2.6
T3	13	35.1	19	50.0
T4	0	0	18	47.4
Lymph node Stage
N0	11	29.7%	0	0	X^2 = 57.002 p < .001
N1	14	37.8%	0	0
N2	8	21.6%	1	2.6
N3	4	10.8%	37	97.4

a American Joint Committee on Cancer (AJCC), χ²; Chi square test, n; number of patients.

Fig. 1 The median and range of thioredoxin-1 level (Trx-1) (ng/ml) in metastatic breast cancer (MBC), non-metastatic breast cancer (NMBC) and control groups.

Fig. 2 The median and range of matrix metalloproteinase-9 level (MMP-9) (ng/ml) in metastatic breast cancer (MBC), non-metastatic breast cancer (NMBC) and control groups.

Fig. 3 The median and range of malondialdehyde level (MDA) (nmol/ml) in metastatic breast cancer (MBC), non-metastatic breast cancer (NMBC) and control groups.

Table 2 Comparison of studied parameters in MBC vs. NMBC patients and control group [Median (Min-Max)].

Biomarkers	Control (n = 15)	NMBC patients (n = 37)	MBC patients (n = 38)
Trx-1 (ng/ml)	22.82 (14.03–43.51)	107.39 (23.03–296.38)^*	313.26 (229.22–426.80)^*^,^#
MMP-9 (ng/ml)	93.84 (3.26–184.42)	438.04 (238.77–510.51)^*	691.66 (465.22–764.13)^*^,^#
MDA (nmol/ml)	2.79 (1.22–7.84)	5.77 (2.01–19.13)^*	10.29 (5.51–27.99)^*^,^#
CEA (ng/ml)	0.50 (0.30–1.10)	1.70 (0.90–3.40)^*	5.78 (0.30–70)^*^,^#
CA-15-3 (U/ml)	5.10 (4.10–6.80)	20.00 (7.00–86.00)^*	84.05 (18.00–443.00)^*^,^#

NMBC; non metastatic breast cancer, MBC; metastatic breast cancer, n; number of subjects; Trx-1, thioredoxin-1; MMP-9, matrix metalloproteinase-9; MDA, malondialdehyde; CA15-3, cancer antigen 15-3; CEA, Carcinoembryonic antigen.

* p < .001 compared with control group.

# p < .001 compared with NMBC patients.

Table 3 Relation between serum thioredoxin-1 (Trx-1), matrix metalloproteinase 9 (MMP-9) and malondialdehyde (MDA) serum levels with clinicopathological parameters in breast cancer patients.

Parameters		n	Trx-1 (ng/ml)	MMP-9 (ng/ml)	MDA (nmol/ml)
			Median (Range)	Median (Range)	Median (Range)
Age (years)	≤50	35	229.22 (23.03–426.80)	8.16 (2.01–14.49)	483.33 (350.10–755.07)
	>50	40	263.51 (45.56–393.43)	8.00 (3.21–27.99)	505.98 (238.77–764.13)
Tumor staging	Stage I	12	95.81 (23.03–216.73)	5.39 (2.80–8.16)	424.46 (350.10–483.33)
	Stage II	12	105.04 (83.23–186.02)	5.74 (2.80–11.40)	428.99 (383.70–474.28)
	Stage III	13	134.01 (50.27–296.38)	6.21 (2.01–19.13)	447.10 (238.77–501.45)
	Stage IV	38	313.27^a (229.22–426.80)	10.29^a (5.51–27.99)	691.67^a (465.22–764.13)
Tumor size (cm)	<2	13	98.59 (23.03–216.73)	5.04 (2.80–8.16)	410.87 (350.10–483.33)
	<5 ≥ 2	12	109.54 (83.23–271.40)	5.89 (2.80–13.62)	433.51 (383.70–655.43)
	≥5	50	294.84^b (50.27–426.80)	9.49^b (2.01–27.99)	646.38^b (238.77–764.13)
Tumor Grading	G1	10	105.85 (60.09–216.73)	5.41 (3.21–8.16)	424.46 (350.10–474.28)
	G2	41	229.22^c (23.03–391.58)	8.05^c (2.01–14.49)	483.33^c (238.77–764.13)
	G3	24	293.51^c (90.40–426.80)	10.00^c,d (4.52–27.99)	614.67^c,d (410.87–736.96)
Lymph node metastasis	Negative	11	100.00 (23.03–216.73)	4.90 (2.80–8.16)	438.04 (350.10–483.33)
	Positive	64	265.56^e (45.56–426.80)	9.05^e (2.01–27.99)	582.97^e (238.77–764.13)

n: number of patients; G: grade.

^asignificant difference as compared with the stages I, II and III at p < .05.

^bsignificant difference as compared with the tumor size < 2 and < 5≥2 at p < .05.

^csignificant difference as compared with G1 at p < .05.

^dsignificant difference as compared with G2 at p < .05.

^esignificant difference as compared with lymph node negative at p < .05.

Fig. 4 Positive correlation between serum thioredoxin-1 (Trx-1) level and matrix metalloproteinase-9 (MMP-9) level in all breast cancer patients.

Fig. 5 Positive correlation between serum thioredoxin-1 (Trx-1) and cancer antigen 15-3 (CA15-3) levels (a) and serum Trx-1 and carcinoembryonic antigen (CEA) levels (b) in all breast cancer patients.

Fig. 6 Positive correlation between serum matrix metalloproteinase-9 (MMP-9) level and cancer antigen 15-3 (CA15-3) level (a) and serum MMP-9 level and carcinoembryonic antigen (CEA) level (b) in breast cancer patients.

Fig. 7 Receiver operating characteristic curve (ROC) for serum thioredoxin-1 (Trx-1) level (a) and for serum matrix metalloproteinase-9 (MMP-9) level (b) for detection of breast cancer metastases.