Indoleamine-2,3-dioxygenase 1/cyclooxygenase 2 expression prediction for adverse prognosis in colorectal cancer

doi:10.3748/wjg.v24.i20.2181

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World Journal of Gastroenterology

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World J Gastroenterol. May 28, 2018; 24(20): 2181-2190
Published online May 28, 2018. doi: 10.3748/wjg.v24.i20.2181

Table 1 Correlation of cytoplasmic indoleamine-2,3-dioxygenase 1 expression with colorectal cancer clinicopathologic parameters

Characteristic	Total	Low IDO1	High IDO1	P-value
Sex				0.074
Male	52	22 (42.3)	30 (57.7)
Female	43	27 (62.8)	16 (37.2)
Age in yr				0.65
≥ 60	30	17 (56.7)	13 (43.3)
< 60	65	32 (49.2)	33 (50.8)
Cancers				0.93
Colon	46	24 (52.2)	22 (47.8)
Rectum	49	25 (51.0)	24 (49.0)
BMI				0.16
≥ 25	20	7 (35.0)	13 (65.0)
< 25	75	42 (56.0)	33 (44.0)
Tumor differentiation				0.47
Moderate and poor	78	42 (54.5)	35 (45.5)
Well	17	7 (41.2)	10 (58.8)
Colon cancer stage				0.52
3	20	12 (60.0)	8 (40.0)
2	26	12 (46.2)	14 (53.8)
T stage				0.69
4	29	14 (48.3)	15 (51.7)
2/3	17	10 (58.8)	7 (41.2)
N stage				0.96
1/2	20	11 (55.0)	9 (45.0)
0	26	13 (50.0)	13 (50.0)
Rectum cancer stage				0.67
3	24	11(45.8)	13 (54.2)
2	25	14 (46.0)	11 (44.0)
T stage				0.68
4	22	12 (55.6)	10 (45.4)
2/3	27	12 (44.4)	15 (55.6)
N stage				0.88
1/2	24	12 (50.0)	12 (50.0)
0	25	13 (52.0)	12 (48.0)
CEA in ng/mL				0.45
> 5	42	24 (57.1)	18 (42.9)
≤ 5	53	25 (47.2)	28 (42.8)
CA19-9 in U/mL				0.22
> 37	17	6 (35.3)	11 (64.7)
≤ 37	78	43 (55.1)	35 (44.9)
CD3 TILs				0.27
High	36	22 (61.1)	14 (38.9)
Low	59	28 (47.5)	31 (42.5)
CD8 TILs				0.96
High	22	12 (54.5)	10 (45.5)
Low	73	38 (52.5)	35 (47.5)
COX2				0.92
High	48	26 (54.2)	22 (45.8)
Low	47	24 (51.1)	23 (48.9)
Treatment group				0.58
Celecoxib	44	25 (56.8)	19 (43.2)
Non-celecoxib	51	25 (49.0)	26 (51.0)

Data are presented as n or n (%). BMI: Body mass index; CA: Cancer antigen; CEA: Carcinoembryonic antigen; COX2: Cyclooxygenase 2; CRC: Colorectal cancer; IDO1: Indoleamine-2,3-dioxygenase 1; TILs: Tumor-infiltrating lymphocytes.

Table 2 Correlation of nuclear indoleamine-2,3-dioxygenase 1 expression with colorectal cancer clinicopathologic parameters

Characteristic	Total	Low IDO1	High IDO1	P-value
Sex				0.70
Male	51	39 (76.5)	12 (33.5)
Female	44	36 (81.8)	8 (19.2)
Age in yr				0.92
> 60	30	24 (80.0)	6 (20.0)
≤ 60	65	51 (78.5)	14 (21.5)
Cancers				0.52
Colon	46	38 (82.6)	18 (17.4)
Rectum	49	37 (75.5)	12 (24.5)
BMI				< 0.001
> 25	20	9 (45.0)	11 (55.0)
≤ 25	75	66 (88.0)	9 (12.0)
Tumor differentiation				0.87
Moderate and poor	78	60 (76.9)	18 (23.1)
Well	17	14 (82.3)	3 (17.7)
Conlon cancer stage				0.98
3	20	17 (85.0)	3 (15.0)
2	26	21 (80.8)	5 (19.2)
T stage				0.71
4	29	23 (19.3)	6 (20.7)
2/3	17	15 (88.2.)	2 (11.8)
N stage				0.98
1/2	20	16 (80.0)	4 (20.0)
0	26	22 (84.6)	4 (15.4)
Rectum cancer stage				0.44
3	24	17 (70.8)	7 (29.2)
2	25	21 (84.0)	4 (16.0)
T stage				0.94
4	22	16 (72.7)	6 (27.3)
2/3	27	21 (77.8)	6 (22.2)
N stage				0.28
1/2	24	16 (66.7)	8 (33.3)
0	25	21(84.0)	4 (16.0)
CEA in ng/mL				0.37
> 5	42	35 (83.3)	7 (16.7)
≤ 5	53	39 (73.6)	14 (26.4)
CA19-9 in U/mL				0.78
> 37	81	41 (50.6)	40 (49.4)
≤ 37	17	8 (47.1)	9 (52.9)
CD3 TILs				0.96
High	36	28 (77.8)	8 (22.2)
Low	59	47 (79.7)	12 (20.3)
CD8 TILs				0.26
High	22	15 (68.2)	7 (31.8)
Low	73	60 (82.2)	13 (17.8)
COX2				0.84
High	48	38 (79.2)	10 (20.8)
Low	47	37 (78.7)	10 (21.3)
Treatment group				0.16
Celecoxib	44	38 (86.4)	6 (13.6)
Non-celecoxib	51	37 (72.5)	14 (27.5)

Table 3 Univariate analysis of the correlation of clinicopathological parameters with overall survival in patients with colorectal carcinoma

	HR	95%CI	P value
Sex, male vs female	0.750	0.399-1.411	0.37
Age in yr, ≤ 60 vs > 60	0.899	0.472-1.714	0.74
Cancer, colon vs rectum	1.279	0.712-2.296	0.41
BMI, > 25 vs ≤ 25	1.579	0.697-3.579	0.21
Tumor differentiation, moderate and poor vs well	2.798	1.373-5.702	0.039
Stage, 3 vs 2	1.003	0.534-1.882	0.99
T stage, T4 vs T2/3	1.418	0.755-2.664	0.27
N stage, N1/2 vs N0	1.005	0.536-1.887	0.99
CEA in ng/mL, > 5 vs ≤ 5	2.137	1.141-4.004	0.025
CA19-9 in U/mL, > 37 vs ≤ 37	1.262	0.547-2.911	0.56
CD3 TILs, high vs low	1.195	0.649-2.198	0.55
CD8 TILs, high vs low	2.096	0.975-4.504	0.018
Nuclear IDO1, high vs low	2.044	0.871-4.798	0.039
Cytoplasmic IDO1, high vs low	1.690	0.901-3.173	0.10
Nuclear and cytoplasmic IDO1, high vs low	2.044	0.871-4.798	0.039
COX2, high vs low	1.235	0.659-2.314	0.51
Nuclear IDO1/COX2, IV vs I/II/III	3.048	0.868-10.7	0.0049
Cytoplasmic IDO1/COX2, IV vs I/II/III	2.109	0.976-4.558	0.022
Treatment group, celecoxib vs non-celecoxib	0.943	0.489-1.826	0.86

BMI: Body mass index; CA: Cancer antigen; CEA: Carcinoembryonic antigen; CI: Confidence interval; COX2: Cyclooxygenase 2; CRC: Colorectal carcinoma; HR: Hazard ratio; IDO1: Indoleamine-2,3-dioxygenase 1; TILs: Tumor infiltrating lymphocytes.

Table 4 Multivariate analysis of the correlation of indoleamine-2,3-dioxygenase 1 with overall survival in patients with Colorectal cancer

	HR	95%CI	P-value
Cytoplasmic IDO1 and COX2, IV vs I/II/III	2.218	1.011-4.48	0.047
Tumor differentiation, poor and moderate vs well	3.473	1.201-10.046	0.022

CI: Confidence interval; COX2: Cyclooxygenase 2; HR: Hazard ratio; IDO1: Indoleamine-2,3-dioxygenase 1.

Table 5 Univariate analysis of the correlation of clinicopathological parameters with overall survival in CRC celecoxib subgroup

	HR	95%CI	P value
Sex, male vs female	0.854	0.329-2.219	0.74
Age in yr, ≤ 60 vs > 60	1.249	0.432-3.609	0.70
Cancer, colon vs rectum	1.034	0.420-2.543	0.94
BMI, > 25 vs ≤ 25	1.328	0.351-5.020	0.71
Tumor differentiation, moderate and poor vs well	7.396	2.749-19.90	0.021
Stage, 3 vs 2	1.075	0.415-2.782	0.88
T stage, T4 vs T2/3	1.389	0.537-3.596	0.50
N stage, N1/2 vs N0	1.075	0.415-2.782	0.88
CEA in ng/mL, > 5 vs ≤ 5	1.934	0.743-5.033	0.21
CA19-9 in m/L, > 37 vs ≤ 37	1.551	0.431-5.575	0.43
CD3 TILs, high vs low	1.02	0.414-2.510	0.97
CD8 TILs, high vs low	2.821	0.774-10.29	0.026
Nuclear IDO1, high vs low	3.023	0.585-15.61	0.041
Cytoplasmic IDO1, high vs low	1.623	0.617-4.267	0.31
Nuclear and cytoplasmic IDO1, high vs low	3.023	0.585-15.61	0.041
COX2, high vs low	1.746	0.672-4.541	0.25
Nuclear IDO1/COX2, IV vs I/II/III	1.885	0.279-12.76	0.38
Cytoplasmic IDO1/COX2, IV vs I/II/III	2.740	0.764-9.831	0.038

Table 6 Multivariate analysis of the correlation of indoleamine-2,3-dioxygenase 1 with overall survival in Colorectal cancer celecoxib subgroup

	HR	95%CI	P-value
Cytoplasmic IDO1 and COX2, IV vs I/II/III	3.210	1.074-9.590	0.037
Tumor differentiation, poor and moderate vs well	11.962	1.526-23.787	0.018

CI: Confidence interval; COX2: Cyclooxygenase 2; HR: Hazard ratio; IDO1: Indoleamine-2,3-dioxygenase 1.

Citation: Ma WJ, Wang X, Yan WT, Zhou ZG, Pan ZZ, Chen G, Zhang RX. Indoleamine-2,3-dioxygenase 1/cyclooxygenase 2 expression prediction for adverse prognosis in colorectal cancer. World J Gastroenterol 2018; 24(20): 2181-2190
URL: https://www.wjgnet.com/1007-9327/full/v24/i20/2181.htm
DOI: https://dx.doi.org/10.3748/wjg.v24.i20.2181