Redox, immune and genetic biomarker system for personalized treatments in colorectal cancer

Table 1 Levels of cytokines, soluble receptors and redox system molecules in healthy subject adenoma subject and tumor patients groups

	HS	Men	Women	Men vs womendifferences
Trx1	107.6 ± 12.2	124.3 ± 22.7	98.0 ± 14.0	NS
RTrx1	2.2 ± 0.2	2.7 ± 0.4	2.0 ± 0.2	NS
sCD30	8.0 ± 0.7	6.7 ± 0.9	8.9 ± 1.0	NS
TGFβ	14800.0 ± 498.2	15150.2 ± 906.5	14598.3 ± 594.8	NS
IL2	53.6 ± 4.8	42.1 ± 5.7	70.0 ± 8.1	NS
IFNγ	69.4 ± 6.9	53.9 ± 9.6	92.0 ± 9.5	NS
IL4	9.4 ± 0.6	8.0 ± 0.8	11.4 ± 0.9	P < 0.00001
IL6	4.1 ± 0.8	2.7 ± 0.6	5.3 ± 1.5	P = 0.001
IL10	5.2 ± 0.7	4.8 ± 0.5	5.9 ± 1.7	NS
sIL2R	250.0 ± 10.4	238.6 ± 12.5	260.6 ± 16.4	P = 0.00009
sIL6R	70.7 ± 4.0	67.4 ± 6.0	73.5 ± 5.4	NS
	AS
Trx1	649.5 ± 60.6	637.9 ± 112.7	656.7 ± 75.5	NS
RTrx1	3.24 ± 0.27	3.4 ± 0.4	3.1 ± 0.37	NS
sCD30	10.7 ± 2.5	8.5 ± 3.1	12.1 ± 3.7	NS
TGFβ	24474.3 ± 665.8	25050.0 ± 1582.4	24114.5 ± 540.8	NS
IL2	39.9 ± 23.5	19.2 ± 1.4	52.8 ± 38.4	NS
IFNγ	98.3 ± 17.5	130.9 ± 35.3	78.0 ± 16.1	NS
IL4	25.5 ± 4.5	15.2 ± 5.4	31.9 ± 5.5	NS
IL6	6.2 ± 2.1	0.5 ± 0.4	9.8 ± 2.8	NS
IL10	7.1 ± 0.9	7.3 ± 2.1	6.9 ± 1.0	NS
sIL2R	295.9 ± 26.7	285.6 ± 50.2	302.3 ± 32.7	NS
sIL6R	146.2 ± 11.2	154.9 ± 20.2	140.7 ± 13.7	NS
	TP
Trx1	1125.0 ± 72.5	1083.7 ± 104.3	1086.3 ± 108.1	NS
RTrx1	3.5 ± 0.5	3.4 ± 0.6	4.4 ± 1.0	NS
sCD30	18.0 ± 2.8	21.3 ± 2.9	17.8 ± 4.0	NS
TGFβ	65331.7 ± 6852.0	69385.9 ± 7400.6	70296.5 ± 16452.3	NS
IL2	16.1 ± 3.6	11.2 ± 1.9	16.1 ± 2.5	NS
IFNγ	140.0 ± 14.4	135.2 ± 7.2	140.0 ± 11.4	NS
IL4	160.5 ± 20.5	186.2 ± 33.8	151.6 ± 60.5	NS
IL6	140.0 ± 46.0	139.5 ± 50.3	176.1 ± 92.0	NS
IL10	31.4 ± 6.4	37.7 ± 9.1	22.2 ± 5.7	NS
sIL2R	532.2 ± 21.8	545.2 ± 29.0	504.2 ± 44.7	NS

HS vs AS: Trx1 P = 0.009; RTrx1 P = 0.008; TGFβ P = 0.04; IFNγ P = 0.01; IL6 P = 0.0004; IL10 P = 0.002; sIL2R P < 0.00001; sIL6R P ≤ 0.00001; HS vs TP: Trx1 P < 0.00001; RTrx1 P < 0.00001; sCD30 P < 0.00001; TGFβ P < 0.00001; IL2 P < 0.00001; IFNγ P < 0.00001; IL4 P < 0.00001; IL6 P < 0.00001; IL10 P < 0.00001; sIL2R P < 0.00001; sIL6R P < 0.00001; IL10 P < 0.00001; sIL2R P < 0.00001; sIL6R P < 0.00001. HS: Healthy subject; AS: Adenoma subject; TP: Tumor patients.

Table 2 FcγRIIa and FcγRIIIa polymorphism frequencies in healthy subjects and tumor patients

	HS	Men	Women		Men	Women		Men	Women
	H/H			H/R			R/R
V/V	38.89	40.00	38.46	9.01	11.11	7.70	8.33	16.67	0.00
V/F	55.55	40.00	61.54	68.18	55.55	76.92	75.00	83.33	66.67
F/F	5.50	20.00	0.00	22.72	33.33	15.38	16.67	0.00	33.33
	TP
V/V	25.00	33.33	0.00	6.67	12.50	0.00	0.00	0.00	0.00
V/F	75.00	66.67	100.00	80.00	75.00	85.71	100.00	100.00	100.00
F/F	0.00	0.00	0.00	13.33	12.50	14.28	0.00	0.00	0.00
	HS vs TP
V/V	P = 0.035	NS	P < 0.0001	NS	NS	P = 0.004	P = 0.0033	P < 0.0001	NS
V/F	P = 0.004	P = 0.0002	P < 0.0001	NS	P = 0.004	NS	P < 0.0001	P < 0.0001	P < 0.0001
F/F	P = 0.017	P < 0.0001	NS	NS	P = 0.0005	NS	P < 0.0001	NS	P < 0.0001

Values are expressed as percentages. The statistical data were obtained by using χ² of goodness-of-fit statistic. Values of P < 0.05 were considered significant. NS: Not significant; HS: Healthy subject; TP: Tumor patients.

Table 3 FcγRIIa and FcγRIIIa biomarkers of the risk of disease progression

			Sensitivity	Specificity	Likelihood ratio		Predictive value
					Positive	Negative	Positive	Negative
Men	No risk
	HH/FF	P < 0.0001	0.00%	80.00%	0.00	1.25	0.00%	40.00%
	RR/VV	P < 0.0001	0.00%	83.33%	0.00	1.20	0.00%	55.56%
	Moderate risk
	HR/FF	P = 0.0005	12.50%	66.67%	0.37	1.31	25.00%	46.15%
	High risk
	HH/VF	P = 0.0002	66.67%	60.00%	1.67	0.56	66.67%	60.00%
	HR/VF	P = 0.004	75.00%	44.44%	1.35	0.56	54.55%	66.67%
	RR/VF	P < 0.0001	100.00%	16.67%	1.20	0.00	44.44%	100.00%
Women	No risk
	HH/VV	P < 0.0001	0.00%	61.54%	0.00	1.62	0.00%	80.00%
	HR/VV	P = 0.004	0.00%	92.31%	0.00	1.08	0.00%	63.16%
	RR/FF	P < 0.0001	0.00%	66.67%	0.00	1.50	0.00%	66.67%
	High risk
	HH/VF	P < 0.0001	100.00%	38.46%	1.62	0.00	20.00%	100.00%
	RR/VF	P < 0.0001	100.00%	33.33%	1.50	0.00	33.33%	100.00%

The statistical data were obtained by using Diagnostic test evaluation/MedCalc-statistical software. Values of P < 0.05 were considered significant.

Table 4 Levels of phenotypic antigen expression in healthy subjects and tumor patients

	HS	Men	Women	TP	Men	Women
CD3	59.8 ± 1.3	60.9 ± 1.8	58.3 ± 1.9	49.0 ± 2.3	46.7 ± 2.8	52.4 ± 4.0
CD8	25.3 ± 0.9	25.0 ± 1.3	26.1 ± 1.2	20.0 ± 1.3	19.2 ± 1.5	21.4 ± 2.3
CD16	12.5 ± 1.1	16.5 ± 1.8	7.7 ± 0.8	15.5 ± 1.3	15.4 ± 1.5	14.7 ± 2.3
CD56	11.8 ± 1.2	14.6 ± 1.9	8.5 ± 0.9	16.4 ± 1.6	17.5 ± 2.0	14.9 ± 2.5
CD57	23.7 ± 1.2	25.9 ± 1.8	21.5 ± 1.3	23.7 ± 1.8	22.3 ± 1.8	26.2 ± 4.0
CD3-CD56+	19.7 ± 0.1	19.7 ± 0.1	19.7 ± 0.1	12.7 ± 3.2	18.0 ± 5.5	7.3 ± 2.1
CD8-CD57+	11.4 ± 1.6	12.4 ± 2.0	8.4 ± 2.2	7.2 ± 3.1	15.5 ± 0.1	4.5 ± 1.9