ALK gene copy number gain and its clinical significance in hepatocellular carcinoma

Table 1 Clinicopathological characteristics of hepatocellular carcinoma patients n (%)

Characteristics	Patients
Total	213 (100)
Age (yr)a
< 49	105 (49.3)
≥ 49	108 (50.7)
Sex
Female	17 (8.0)
Male	196 (92.0)
Grade
I	19 (8.9)
II	97 (45.5)
III	91 (42.7)
IV	6 (2.8)
Stage
I + II	174 (81.7)
III + IV	39 (18.3)
Relapse
No	83 (39.0)
Yes	130 (61.0)
AFP (ng/mL)
< 400	125 (58.7)
≥ 400	88 (41.3)
Child-Pugh classification
A	195 (91.5)
B	16 (7.5)
C	2 (0.9)
HBV DNA
Positive	113 (53.1)
Negative	100 (46.9)
Postoperative platelet count
< 100 × 109/L	35 (16.4)
≥ 100 × 109/L	178 (83.6)

^aMedian: 49, range: 25-75 years. AFP: Alpha fetoprotein; HBV: Hepatitis B virus.

Table 2 Association between anaplastic lymphoma kinase copy number gain and clinicopathological characteristics of hepatocellular carcinoma patients n (%)

Characteristics	Total cases	ALK/CNG		P value
		Positive (28 cases)	Negative (185 cases)
Age (yr)
< 49	105	12 (11.4)	93 (88.6)	0.465
≥ 49	108	16 (14.8)	92 (85.2)
Sex
Female	17	3 (17.6)	14 (82.4)	0.843
Male	196	25 (12.8)	171 (87.2)
Grade
I + II	116	12 (10.3)	104 (89.7)	0.186
III + IV	97	16 (16.5)	81 (83.5)
Stage
I + II	174	21 (12.1)	153 (87.9)	0.326
III + IV	39	7 (17.9)	32 (82.1)
Relapse
No	83	13 (15.7)	70 (84.3)	0.385
Yes	130	15 (11.5)	115 (88.5)
AFP (ng/mL)
< 400	125	19 (15.2)	106 (84.8)	0.290
≥ 400	88	9 (10.2)	79 (89.8)
Child-Pugh- classification
A	195	25 (12.8)	170 (87.2)	0.922
B + C	18	3 (16.7)	15 (83.3)
HBV DNA
Positive	113	17 (15.0)	96 (85.0)	0.383
Negative	100	11 (11.0)	89 (89.0)
Postoperative platelet count
< 100 × 109/L	35	2 (5.7)	33 (94.3)	0.250
≥ 100 × 109/L	178	26 (14.6)	152 (85.4)

ALK/CNG: Anaplastic lymphoma kinase copy number gain; AFP: Alpha fetoprotein; HBV: Hepatitis B virus.

Table 3 Cox regression analysis of progression-free-survival in hepatocellular carcinoma patients

Variables	Subset	HR (95%CI)	P value
Univariate analysis (n = 213)
Age (yr)	< 49 vs≥ 49	1.153 (0.834-1.596)	0.389
Sex	Female vs male	1.464 (0.770-2.783)	0.245
AFP (ng/mL)	< 400 vs≥ 400	1.219 (0.879-1.690)	0.236
Grade	I + II vs III + IV	1.335 (0.966-1.847)	0.080
Stage	I + II vs III + IV	1.926 (1.304-2.845)	0.001
ALK/CNG	Yes vs no	1.598 (1.001 -2.552)	0.049
Child-Pugh classification	A vs B + C	2.165 (1.300-3.608)	0.002
HBV DNA	Positive vs negative	1.067 (0.771-1.476)	0.696
Postoperative plateletcount	< 100 × 109/L vs≥ 100 × 109/L	1.267 (0.839-1.914)	0.260
Multivariate analysis (n = 213)
Stage	I + II vs III + IV	1.775 (1.179-2.673)	0.006
ALK/CNG	Yes vs no	1.596 (1.008-2.526)	0.046
Child-Pugh classification	A vs B + C	1.744 (1.021-2.979)	0.042

ALK/CNG: Anaplastic lymphoma kinase copy number gain; AFP: Alpha fetoprotein; HBV: Hepatitis B virus.