Significance of downregulation of liver fatty acid-binding protein in hepatocellular carcinoma

doi:10.3748/wjg.v20.i46.17541

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World Journal of Gastroenterology

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Observational Study

World J Gastroenterol. Dec 14, 2014; 20(46): 17541-17551
Published online Dec 14, 2014. doi: 10.3748/wjg.v20.i46.17541

Table 1 Clinicopathological characteristics of the cases n (%)

Characteristics	n = 146
Age (yr)	64.2 ± 10.1
36-60	49 (33.6)
61-70	51 (34.9)
71-82	46 (31.5)
Gender
Male	105 (72.0)
Female	41 (28.0)
Viral infection
HBV	32 (22.0)
HCV	98 (67.1)
NonB nonC	16 (10.9)
Child-Pugh classification
A	139 (95.2)
B	7 (4.8)
C	0 (0)
Background liver tissue
Normal	4 (2.8)
Chronic hepatitis	56 (39.7)
Liver cirrhosis	81 (57.5)
Tumor size (mm)	27.3 ± 25.4
8-10	7 (4.8)
11-20	78 (53.4)
21-30	29 (19.9)
31-250	32 (21.9)
Differentiation
Well	33 (22.6)
Moderate	93 (63.7)
Poor	20 (13.7)
Pseudoglandular pattern
Absent	97 (66.4)
Present	49 (33.6)
Nuclear grade
Low	116 (79.5)
High	30 (20.5)
Fatty change
Absent	121 (82.9)
Present	25 (17.1)
Inflammation
Absent	75 (51.4)
Present	71 (48.6)
Fibrosis
Absent	104 (71.2)
Present	42 (28.8)
Cholestasis
Absent	95 (65.0)
Present	51 (35.0)
Tumor stage
1	65 (44.5)
2	61 (41.8)
3	16 (11.0)
4	4 (2.7)
L-FABP immunostaining
Negative	16 (10.9)
Positive	130 (89.1)
CK 7 immunostaining
Negative	68 (46.6)
Positive	78 (53.4)
CK 19 immunostaining
Negative	136 (93.2)
Positive	10 (6.8)
β-catenin immunostaining
Negative	101 (69.2)
Positive	45 (30.8)
GS immunostaining
Negative	110 (75.3)
Positive	36 (24.7)
SAA immunostaining
Negative	136 (93.2)
Positive	10 (6.8)

HBV: Hepatitis B virus; HCV: Hepatitis C virus; L-FABP: Liver fatty acid-binding protein; CK: Cytokeratin; GS: Glutamine synthetase; SAA: Serum amyloid A. Background liver tissue could not be evaluated in five cases.

Table 2 Correlation between liver fatty acid-binding protein downregulation pattern and tumor size n (%)

	Tumor ≤2 cm n = 11	Tumor > 2 cm n = 5	P value
Focal downregulation (n = 10)	9 (81.8)	1 (20.0)	0.036^a
Diffuse downregulation (n = 6)	2 (18.2)	4 (80.0)	0.036^a

^aP < 0.05, small HCC cases vs large HCC cases. HCC: Hepatocellular carcinoma.

Table 3 Relation between liver fatty acid-binding protein expression and clinical features n (%)

Characteristics	Tumor size ≤2 cm		P value	Tumor size > 2 cm		P value	Total		P value
Characteristics	L-FABP negative n = 11	L-FABP positive n = 74		L-FABP negative n = 5	L-FABP positive n = 56	P value	L-FABP negative n = 16	L-FABP positive n = 130	P value
Age	71.3 ± 7.6	63.4 ± 9.3	P value	0.009^b	54.6 ± 10.8	64.8 ± 10.7	0.044^a	66.0 ± 11.5	64.0 ± 9.9	0.462
Gender			0.729			0.320			0.771
Male	7 (63.6)	52 (70.3)		5 (100)	41 (73.2)		12 (75.0)	93 (71.5)
Female	4 (36.4)	22 (29.7)		0 (0)	15 (26.8)		4 (25.0)	37 (28.5)
Viral infection
HBV	3 (27.3)	16 (21.6)	0.465	2 (40.0)	11 (19.6)	0.286	5 (31.3)	27 (20.8)	0.253
HCV	7 (63.6)	50 (67.6)	0.732	3 (60.0)	38 (67.9)	0.806	10 (62.5)	88 (67.7)	0.761
NonB nonC	1 (9.1)	8 (10.8)	0.671	0 (0)	7 (12.5)	0.531	1 (6.2)	15 (11.5)	0.451
Child-Pugh classification			0.499			0.540			0.343
A	11 (100)	71 (95.9)		5 (100)	52 (92.9)		16 (100)	123 (94.6)
B	0 (0)	3 (4.1)		0 (0)	4 (7.1)		0 (0)	7 (5.4)
C	0 (0)	0 (0)		0 (0)	0 (0)		0 (0)	0 (0)

^aP < 0.05, 54.6 ± 10.8 years vs 64.8 ± 10.7 years;

^bP < 0.01, 71.3 ± 7.6 years vs 63.4 ± 9.3 years. L-FABP: Liver fatty acid-binding protein; HBV: Hepatitis B virus; HCV: Hepatitis C virus.

Table 4 Relation between liver fatty acid-binding protein expression and pathological features n (%)

Characteristics	Tumor size ≤2 cm		P value	Tumor size > 2 cm		P value	Total		P value
Characteristics	L-FABP negative n = 11	L-FABP positive n = 74		L-FABP negative n = 5	L-FABP positive n = 56	P value	L-FABP negative n = 16	L-FABP positive n = 130	P value
Tumor size (mm)	16.0 ± 2.1	15.8 ± 3.3	P value	0.566	45.4 ± 29.5	43.3 ± 33.6	0.931	25.2 ± 20.8	27.6 ± 26.0	0.652
Differentiation			0.032^a			0.766			0.110
Well	0 (0.0)	26 (35.1)		0 (0.0)	7 (12.5)		0 (0.0)	33 (25.4)
Moderate	10 (90.9)	43 (58.1)		4 (80.0)	36 (64.3)		14 (87.5)	79 (60.8)
Poor	1 (9.1)	5 (6.8)		1 (20.0)	13 (23.2)		2 (12.5)	18 (13.8)
Pseudoglandular pattern			0.478			0.218			0.461
Absent	8 (72.7)	49 (66.2)		2 (40.0)	38 (67.9)		10 (62.5)	87 (66.9)
Present	3 (27.3)	25 (33.8)		3 (60.0)	18 (32.1)		6 (37.5)	43 (33.1)
Nuclear grade			0.299			0.641			0.424
Low	8 (72.7)	62 (83.8)		4 (80.0)	42 (75.0)		12 (75.0)	104 (80.0)
High	3 (27.3)	12 (16.2)		1 (20.0)	14 (25.0)		4 (25.0)	26 (20.0)
Fatty change			0.659			0.436			0.458
Absent	9 (81.8)	60 (81.1)		5 (100.0)	47 (83.9)		14 (87.5)	107 (82.3)
Present	2 (18.2)	14 (18.9)		0 (0.0)	9 (16.1)		2 (12.5)	23 (17.7)
Inflammation			0.009^b			0.660			0.039^a
Absent	9 (81.8)	29 (39.2)		3 (60.0)	34 (60.7)		12 (75.0)	63 (48.5)
Present	2 (18.2)	45 (60.8)		2 (40.0)	22 (39.3)		4 (25.0)	67 (51.5)
Fibrosis			0.160			0.466			0.105
Absent	10 (90.9)	53 (71.6)		4 (80.0)	37 (66.1)		14 (87.5)	90 (69.2)
Present	1 (9.1)	21 (28.4)		1 (20.0)	19 (33.9)		2 (12.5)	40 (30.8)
Cholestasis			0.224			0.369			0.120
Absent	9 (81.8)	48 (64.9)		4 (80.0)	34 (60.7)		13 (81.3)	82 (63.1)
Present	2 (18.2)	26 (35.1)		1 (20.0)	22 (39.3)		3 (18.7)	48 (36.9)
Tumor stage			0.833			0.789			0.646
1	8 (72.7)	56 (75.7)		0 (0.0)	1 (1.8)		8 (50.0)	57 (43.8)
2	3 (27.3)	18 (24.3)		3 (60.0)	37 (66.1)		6 (37.5)	55 (42.3)
3	0 (0.0)	0 (0.0)		2 (40.0)	14 (25.0)		2 (12.5)	14 (10.8)
4	0 (0.0)	0 (0.0)		0 (0.0)	4 (7.1)		0 (0.0)	4 (3.1)
Background liver tissue			0.649			0.394			0.301
Normal	0 (0.0)	0 (0.0)		0 (0.0)	4 (7.7)		0 (0.0)	4 (3.2)
CH	3 (27.3)	25 (34.2)		2 (40.0)	26 (50.0)		5 (31.3)	51 (40.8)
LC	8 (72.7)	48 (65.8)		3 (60.0)	22 (42.3)		11 (68.7)	70 (56.0)

^aP < 0.05, L-FABP-negative small HCCs vs L-FABP-positive small HCCs;

^bP < 0.01, L-FABP-negative cases vs in L-FABP-positive cases. Background liver tissue could not be evaluated in five cases. L-FABP: Liver fatty acid-binding protein; CH: Chronic hepatitis; LC: Liver cirrhosis.

Table 5 Relation between liver fatty acid-binding protein expression and other immunohistochemical markers n (%)

Immunostaining	Tumor size ≤2 cm		P value	Tumor size > 2 cm		P value	Total		P value
Immunostaining	L-FABP negative n = 11	L-FABP positive n = 74		L-FABP negative n = 5	L-FABP positive n = 56	P value	L-FABP negative n = 16	L-FABP positive n = 130	P value
CK 7			P value	0.430			0.515			0.512
Negative	4 (36.4)	33 (44.6)		3 (60.0)	28 (50.0)		7 (43.8)	61 (46.9)
Positive	7 (63.6)	41 (55.4)		2 (40.0)	28 (50.0)		9 (56.2)	69 (53.1)
CK 19			0.423			0.703			0.301
Negative	11 (100)	68 (91.9)		5 (100)	52 (92.9)		16 (100)	120 (92.3)
Positive	0 (0)	6 (8.1)		0 (0)	4 (7.1)		0 (0)	10 (7.7)
β-catenin			0.009^b			0.433			0.073
Negative	4 (36.4)	57 (77.0)		4 (80.0)	36 (64.3)		8 (50.0)	93 (71.5)
Positive	7 (63.6)	17 (23.0)		1 (20.0)	20 (35.7)		8 (50.0)	37 (28.5)
GS			0.000^b			0.393			0.001^b
Negative	3 (27.3)	62 (83.8)		3 (60.0)	42 (75.0)		6 (37.5)	104 (80.0)
Positive	8 (72.7)	12 (16.2)		2 (40.0)	14 (25.0)		10 (62.5)	26 (20.0)
SAA			0.268			0.918			0.301
Negative	11 (100)	65 (87.8)		5 (100)	55 (98.2)		16 (100)	120 (92.3)
Positive	0 (0)	9 (12.2)		0 (0)	1 (1.8)		0 (0)	10 (7.7)

^bP < 0.01, L-FABP-negative small HCCs vs L-FABP-positive small HCCs. L-FABP: Liver fatty acid-binding protein; CK: Cytokeratin; GS: Glutamine synthetase; SAA: Serum amyloid A; HCC: Hepatocellular carcinoma.

Citation: Inoue M, Takahashi Y, Fujii T, Kitagawa M, Fukusato T. Significance of downregulation of liver fatty acid-binding protein in hepatocellular carcinoma. World J Gastroenterol 2014; 20(46): 17541-17551
URL: https://www.wjgnet.com/1007-9327/full/v20/i46/17541.htm
DOI: https://dx.doi.org/10.3748/wjg.v20.i46.17541