Clinical and prognostic significance of CC chemokine receptor type 8 protein expression in gastrointestinal stromal tumors

Table 1 Correlations between clinicopathological features and CC chemokine receptor type 8 expression in gastrointestinal stromal tumors

Characteristic	n	CCR8-, n (%)	CCR8+, n (%)	Pearson χ2	P value
Total	125	51 (40.80 )	74 (59.20)
Gender				1.439	0.230
Male	62	22 (35.48)	40 (64.52)
Female	63	29 (46.03)	34 (53.97)
Age				2.268	0.132
≤ 60 yr	81	37 (45.68)	44 (54.32)
> 60 yr	44	14 (31.82)	30 (68.18)
Tumor size, cm				8.999	0.01
< 5	25	16 (64.00)	9 (36.00)
5-10	80	30 (37.50)	50 (62.50)
> 10	20	5 (25.00)	15 (75.00)
Mitotic index, per 50 HPFs				8.196	0.017
0-5	70	34 (48.57)	36 (51.43)
6-10	30	13 (43.33)	17 (56.67)
> 10	25	4 (16.00)	21 (84.00)
Gross classification				1.035	0.309
Single nodule	92	40 (43.48)	52 (56.52)
Multiple nodules	33	11 (33.33)	22 (66.67)
Tumor location				11.673	0.003
Stomach	69	34 (49.28)	35 (50.72)
Intestine	42	9 (21.42)	33 (78.58)
Others	14	9 (64.29)	5 (35.71)
AFIP-Miettinen risk classification				4.308	0.038
Very low–Moderate risk	85	40 (47.06)	45 (52.94)
High risk	40	11 (27.50)	29 (72.50)

P < 0.05. CCR8: A proliferation-inducing ligand; GIST: Gastrointestinal stromal tumors; HPFs: High-power fields.

Table 2 Univariate and multivariate analysis of factors affecting prognosis in GISTs

Variable		Univariate analysis				Multivariate analysis
	Yr	P > |z|		95%CI		P > |z|		95%CI
Gender
Male vs Female	10/5	0.448/0.140	0.754/0.547	0.364/0.246	1.563/1.219
Age in yr
≤ 60 vs > 60	10/5	0.964/0.524	0.983/0.767	0.469/0.339	2.060/1.735
Tumor size in cm
< 5 vs 5-10 vs > 10	10/5	0.004/0.019	2.417/2.160	1.336/1.137	4.371/4.102	0.0470	1.876	1.010	3.487
Mitotic index/5 HPFs
0-5 vs 6-10 vs > 10	10/5	< 0.001/< 0.001	2.696/2.727	1.687/1.645	4.310/4.522	0.002/0.001	2.177/2.335	1.345/1.401	3.523/3.889
Gross classification
Single vs Multiple	10/5	0.300/ 0.315	1.569/1.601	0.670/ 0.639	3.677/4.009
Tumor location
Stomach vs Intestine	10/5	0.185/0.281	1.396/1.339	0.853/0.787	2.284/2.279
CCR8 expression
High vs Low	10/5	0.011/0.005	2.738/4.651	1.261/1.593	5.949/13.580	0.037/0.027	2.663/3.432	1.062/1.151	6.677/10.232

P < 0.05. CCR8: A proliferation-inducing ligand; GISTs: Gastrointestinal stromal tumors; HPFs: High-power fields; CI: Confidence interval.

Table 3 Gene Ontology (Biological Process) enrichment of CC chemokine receptor type 8

Term	Count %		P value
GO: 0070098~chemokine mediated signaling pathway	20	26.67	1.25E-43
GO: 0060326~cell chemotaxis	20	10.93	3.99E-37
GO:0006935~chemotaxis	21	4.28	7,57E-32
GO: 0030595~leukocyte chemotaxis	17	13.08	2.39E-31
GO: 0048247~lymphocyte chemotaxis	14	31.11	1.33E-29
GO: 0010469~regulation of signaling receptor activity	20	3.47	6.99E-28
GO: 0035821~modification of morphology or physiology of other organism	16	8.79	1.02E-26
GO: 0031640~killing of cells of other organism	14	15.73	4.18E-26
GO: 0061844~antimicrobial humoral immune response mediated by antimicrobial peptide	14	13.08	3.62E-25
GO: 0006954~inflammatory response	18	3.73	9.59E-25
GO: 0002685~regulation of leukocyte migration	15	8.57	9.59E-25
GO: 0002687~positive regulation of leukocyte migration	14	11.02	2.56E-24
GO: 0007186~G protein-coupled receptor signaling pathway	21	1.68	3.62E-24
GO: 0002690~positive regulation of leukocyte chemotaxis	13	14.29	8.72E-24
GO: 0006955~immune response	21	1.34	3.10E-22
GO: 0097529~myeloid leukocyte migration	12	11.65	7.52E-21
GO: 0002548~monocyte chemotaxis	10	24.39	4.97E-20
GO: 0071347~cellular response to interleukin-1	12	9.68	5.34E-20
GO: 0006592~defense response	19	1.54	8.02E-20
GO: 0032103~positive regulation of response to external stimulus	14	4.81	8.98E-20

The top 20 terms were listed on the basis of their P values if there were > 20 terms in the category. GO: Gene Ontology.

Table 4 Kyoto Encyclopedia of Genes and Genomes enrichment of CC chemokine receptor type 8

Term	Count	%	P value
Hsa04062: Chemokine signaling pathway	2.10E+01	11.60	2.30E-41
Hsa04060: Cytokine-cytokine receptor infiltration	2.10E+01	7.98	2.03E-38
Hsa04064: NF kappa B signaling pathway	7.00E+00	7.53	9.35E-11
Hsao04620: Toll-like receptor signaling pathway	7.00E+00	6.86	1.30E-10
Hsa05323: Rheumatoid arthritis	6.00E+00	7.14	2.86E-09
Hsa04668: TNF signaling pathway	6.00E+00	S.56	1.00E-08
Hsa04657: lL-17 signaling pathway	5.00E+00	S.43	2.56E-07
Hsa04623: Cytosolic DNA-sensing pathway	4.00E+00	6.45	2.95E-06
Hsa05132: Salmonella infection	4.00E+00	4.76	1.90E-04
Hsa05120: Epithelial cell signaling in Helicobacter pylori infection	3.00E+00	4.55	2.40E-03
Hsa05164: Influenza A	3.00E+00	1.79	2.40E-03
Hsa04621: N0D-like receptor signaling pathway	3.00E+00	1.88	2.70E-03
Hsa05167: Kaposi’s sarcoma-associated herpesvirus infection	3.00E+00	1.81	3.62E-24
Hsa04672: Intestinal immune network for IgA production	2.00E+00	4.55	2.80E-03
Hsa05134: Legionellosis	2.00E+00	3.70	3.80E-03

The top 15 terms were listed on the basis of their P values if there were > 15 terms in the category. KEGG: Kyoto Encyclopedia of Genes and Genomes; GO: Gene Ontology; TNF: Tumor necrosis factor; NF: Nuclear factor.