Clinical significance of nerve growth factor and tropomyosin-receptor-kinase signaling pathway in intrahepatic cholangiocarcinoma

Table 1 Correlations between nerve growth factor/tropomyosin-receptor-kinase expression and clinicopathologic parameters

Clinicopathologic parameters		n	NGF		P value1	TrkA		P value1
			low	high		low	high
Age	< 65 yr	62	44	18	0.640	49	13	0.850
	≥ 65 yr	21	16	5		13	4
Gender	Male	44	30	14	0.373	32	12	0.099
	Female	39	30	9		34	5
Tumor size	< 5 cm	37	24	13	0.220	28	9	0.438
	≥ 5 cm	46	36	10		38	8
Differentiation	Well	19	9	10	0.024	20	5	0.228
	Moderately	39	32	7		34	5
	Poorly	25	19	6		12	7
T stage	T1	40	29	11	0.200	33	7	0.428
	T2	20	17	3		16	4
	T3	23	14	9		17	6
	T4	0	0	0		0	0
N stage	N0	57	40	17	0.520	46	11	0.695
	N1	26	20	6		20	6
M stage	M0	79	57	22	0.900	63	16	0.823
	M1	4	3	1		3	1
TNM stage	I	31	22	9	0.948	26	5	0.470
	II	10	9	1		8	2
	III	16	9	7		12	4
	IVa	22	17	5		17	5
	IVb	4	3	1		3	1
Satellites	N	63	45	18	0.754	51	12	0.572
	P	20	15	5		15	5
Macrovascular invasion	N	80	57	23	0.158	63	17	0.236
	P	3	3	0		3	0
Microvascular invasion	N	67	48	19	0.786	52	15	0.357
	P	16	12	4		14	2
Intraneural invasion	N	73	53	20	0.864	62	11	0.003
	P	10	7	3		4	6
HBV	N	73	51	22	0.146	57	16	0.347
	P	10	9	1		9	1
Cirrhosis	N	67	48	19	0.786	53	14	0.847
	P	16	12	4		13	3

¹χ² test. NGF: Nerve growth factor; TrkA: Tropomyosin-receptor-kinase; HBV: Hepatitis B virus; N: Negative; P: Positive.

Table 2 Univariate analysis of clinicopathologic features for overall survival

Clinicopathologic parameters		Median	Survival	P value1
Age	< 65 yr	46.2	39.5%	0.776
	≥ 65 yr	59.9	60.3%
gender	male	46.7	42.6%	0.364
	female	51.5	43.5%
Tumor size	< 5 cm	57.4	50.2%	0.029
	≥ 5 cm	40.6	36.1%
Differentiation	Well	54.5	49.9%	0.587
	Moderately	47.8	40.4%
	Poorly	43.6	40.7%
T stage	T1	52.7	49.0%	0.411
	T2	58.9	60.0%
	T3	33.0	23.4%
	T4	0.0	0.0%
N stage	N0	58.7	53.3%	0.002
	N1	17.6	14.0%
M stage	M0	51.8	45.5%	0.004
	M1	7.8	0.0%
TNM stage	I	62.4	60.4%	0.004
	II	73.0	77.8%
	III	46.6	36.8%
	IV	17.2	13.6%
Satellites	Negative	50.0	47.1%	0.132
	Positive	31.3	31.4%
Macrovascular invasion	Negative	49.7	42.9%	0.290
	Positive	24.3	33.3%
Microvascular invasion	Negative	49.5	43.9%	0.445
	Positive	44.7	41.8%
Intraneural invasion	Negative	47.2	41.5%	0.678
	Positive	55.7	52.5%
NGF	Negative	54.2	49.4%	0.201
	Positive	36.4	29.6%
TrkA	Negative	48.9	42.7%	0.483
	Positive	44.6	41.6%
NGF + TrkA	Negative	53.1	46.5%	0.030
	Positive	18.0	24.6%

¹Log-rank test. NGF: Nerve growth factor; TrkA: Tropomyosin-receptor-kinase.

Table 3 Multivariate analysis of clinicopathologic features

Factor	Category	HR	95%CI	P value1
Tumor size	< 5 cm	1.00
	≥ 5 cm	2.00	0.8-3.9	0.157
Differentiation	Well	1.00
	Moderately	0.74	0.3-2.1	0.578
	Poorly	1.65	0.6-4.3	0.335
T stage	T1 + T2	1.00		0.550
	T3 + T4	1.25	0.6-2.6
N stage	N0	1.00		0.015
	N1	3.15	1.3-7.9
M stage	M0	1.00		0.200
	M1	2.18	0.7-7.2
Satellites	Negative	1.00		0.533
	Positive	0.76	0.3-1.8
Macrovascular invasion	Negative	1.00		0.245
	Positive	2.61	0.5-13.2
Microvascualr invasion	Negative	1.00		0.092
	Positive	2.15	0.9-5.2
Intraneural invasion	Negative	1.00		0.927
	Positive	0.95	0.3-2.9
NGF + TrkA	Negative	1.00		0.010
	Positive	2.87	1.3-6.4

¹Cox proportional hazards regression. NGF: Nerve growth factor; TrkA: Tropomyosin-receptor-kinase.