Raf kinase inhibitor protein combined with phosphorylated extracellular signal-regulated kinase offers valuable prognosis in gastrointestinal stromal tumor

Table 1 Relationship between proteins expression and clinical and pathological characteristics of gastrointestinal stromal tumors

Characteristic	n	RKIP			P-ERK			P-MEK
		Negative	Positive	P valuea	Negative	Positive	P valuea	Negative	Positive	P valuea
Sex
Male	36	16	20	0.652	16	20	0.716	22	14	0.365
Female	30	15	15		12	18		15	15
Age in yr
> 56	33	17	16	0.459	13	20	0.618	15	18	0.083
≤ 56	33	14	19		15	18		22	11
Tumor location
Stomach	37	20	17	0.585	16	21	0.902	21	16	0.224
Duodenum	12	4	8		4	8		4	8
Jejunoileum	15	6	9		7	8		11	4
Colon	2	1	1		1	1		1	1
Tumor size in cm
< 2	12	1	11	< 0.001	8	4	0.009	7	5	0.353
2-5	20	5	15		12	8		14	6
6-10	19	14	5		6	13		10	9
> 10	15	11	4		2	13		6	9
NIH risk grade
Very low	10	2	8	< 0.001	7	3	0.004	7	3	0.319
Low	20	3	17		13	7		11	9
Moderate	11	8	3		3	8		8	3
High	25	18	7		5	20		11	14
Mitotic figures as /50 HPFs
0	11	3	8	0.074	5	6	0.015	5	6	0.604
1-4	37	15	22		21	16		22	15
5-10	7	5	2		1	6		5	2
> 10	11	8	3		1	10		5	6
Mucosal invasion
Yes	34	21	13	0.013	10	24	0.027	18	16	0.599
No	32	10	22		18	14		19	13

^aRaf kinase inhibitory protein (RKIP)-positive percentage were compared using the χ² test, P < 0.05 were considered statistically significant.

HPFs: High-power fields; NIH: National Institutes of Health; P-ERK: Phosphorylated extracellular-signal regulated kinase; P-MEK: Phosphorylated mitogen-activated protein kinase\ERK kinase.

Table 2 Correlations among proteins expression

Protein expressions	Negative	P-ERK positive	Correlation and P value	Negative	P-MEK positive	Correlation and P value
RKIP
Negative	3	26	Ca = -0.575	11	18	C = -0.323
Positive	25	12	P < 0.001	26	11	P = 0.008

^aC: Correlation coefficient value is calculated using Spearman‘s rho test, P < 0.05 were considered statistically significant.

P-ERK: Phosphorylated-extracellular-signal regulated kinase; P-MEK: Phosphorylated-mitogen-activated protein kinase\ERK kinase; RKIP: Raf kinase inhibitory protein.

Table 3 Analysis of factors affecting prognosis of gastrointestinal stromal tumors in Cox proportional-hazards regression models for overall survival, n = 63

Characteristic	n	Univariatea			Multivariate1
		HR	95%CI	P value	B	Exp (B)	P value
Sex
Male	34	0.87	0.32-2.34	0.783	0.004	1.004	0.994
Female	29
Age in yr
> 56	30	0.99	0.96-1.03	0.751	-0.011	0.989	0.609
≤ 56	33
Tumor location
Stomach	36	3.86	1.23-12.18	0.021	0.669	1.953	0.057
Duodenum	12
Jejunoileum	15
Tumor size in cm
< 2	11	2.32	1.32-4.07	0.003	0.734	2.083	0.037
2-5	19
6-10	18
> 10	14
NIH risk grade
Very low	10	2.32	1.32-4.07	0.002	1.393	4.025	0.014
Low	19
Moderate	10
High	24
Mitotic figures as /50 HPFs
0	11	1.7	1.06-2.70	0.026	0.179	1.196	0.505
1-4	36
5-10	5
> 10	11
RKIP expression
Positive	35	0.14	0.04-0.50	0.002	-2.064	0.127	0.061
Negative	28
P-ERK expression
Positive	36	3.63	1.03-12.73	0.044	1.761	5.821	0.041
Negative	27
P-MEK expression
Positive	28	1.78	0.66-4.79	0.252
Negative	35
RKIP and P-ERK co-expression2
Positive	25	0.34	012-0.94	0.037	2.427	11.32	0.044
Negative	38

¹Analysed factors were sex, age, tumor location, tumor size, National Institutes of Health (NIH) risk grades, mitotic figures, raf kinase inhibitory protein (RKIP), phosphorylated-extracellular-signal regulated kinase (P-ERK) expressions, RKIP and P-ERK co-expressions.

²Based on the expression of RKIP and P-ERK proteins in gastrointestinal stromal tumors specimens, we defined the cases with RKIP (-) and P-ERK (+) as negative, while the cases with RKIP (+) or P-ERK (-) as positive.

^aLog-rank test; P < 0.05 were considered statistically significant.

HPFs: High-power fields; HR: Hazard ratio; MAPK: Mitogen-activated protein kinase; P-MEK: Phosphorylated-MAPK\ERK kinase.

Table 4 Multivariate analysis of prognostic factors for overall survival of gastrointestinal stromal tumors with two different sets of risk factors, n = 63

Characteristic	n	Multivariate1			Multivariate2
		HR	95%CI	P valuea	HR	95%CI	P valuea
Tumor location
Stomach	36	2.59	0.69-9.69	0.156	4.13	1.07-15.98	0.04
Duodenum	12
Jejunoileum	15
Tumor size in cm
< 2	11	1.92	0.93-3.96	0.079	1.17	0.52-2.62	0.71
2-5	19
6-10	18
> 10	14
Mitotic figures as /50 HPFs
0	11	1.22	0.71-2.10	0.472	1.28	0.75-2.18	0.361
1-4	36
5-10	5
> 10	11
RKIP expression
Positive	35				0.13	0.03-0.66	0.014
Negative	28
P-ERK expression
Positive	36				0.91	0.19-4.32	0.909
Negative	27

¹Analysed factors were tumor location, tumor size, mitotic figures; above are all the risk factors included in NIH 2008 Risk Grade System.

²Analysed factors were tumor location, tumor size, mitotic figures, raf kinase inhibitory protein (RKIP) expressions and phosphorylated-extracellular-signal regulated kinase (P-ERK) expressions.

^aP < 0.05 were considered statistically significant.

HPFs: High-power fields; HR: Hazard ratio; MAPK: Mitogen-activated protein kinase; P-MEK: Phosphorylated MAPK\ERK kinase.