Overexpressed pepsinogen C is associated with poor prognosis in human hepatocellular carcinoma: a tissue microarray study

Figures & data

Figure 1 Pepsinogen C (PGC) expression in HCC and adjacent non-tumor tissues. (A) Representative immunohistochemistry images of high Pepsinogen C (PGC) expression and low PGC expression in HCC and adjacent non-tumor tissues. PGC was expressed predominantly in the cytoplasm. The upper figures were 100× and the down figures were 400×. Scale bar=50 μm. (B) The staining scores of PGC expression between HCC and non-tumor tissues (****P<0.0001). (C) The staining scores of PGC expression between the relapse group and the non-relapse group (****P<0.0001).

Table 1 Associations between Pepsinogen C expression and clinical characteristics

Clinical Characteristics	Pepsinogen C expression		χ^2	P-value^a
	High (n=40)	Low (n=35)
Gender
Male	34	27	0.7590	0.384
Female	6	8
Age (year)
<55	23	17	0.5979	0.439
≥55	17	18
HBsAg
Negative	6	6	0.0638	0.801
Positive	34	29
ALT (U/L)
≤40	19	18	0.1153	0.734
>40	21	17
AFP (ng/mL)
≤20	13	12	0.0268	0.870
>20	27	23
Cirrhosis
Negative	4	5	0.3247	0.726^b
Positive	36	30
Tumor size (cm)
<5	13	21	5.6963	0.017
≥5	27	14
Tumor number
Solitary	32	29	0.1004	0.751
Multiple	8	6
Encapsulation
Incomplete	30	9	18.1662	<0.0001
Complete	10	26
Differentiation
I–II	26	23	0.0042	0.948
III–IV	14	12

Notes: ^aChi-squared test. ^bFisher’s exact test. Bold values represent  statistical significance.

Figure 2 Overall survival and disease-free survival times of 75 pairs of HCC and adjacent non-tumor tissues using Kaplan–Meier analysis. (A) Overall survival (OS) for Pepsinogen C (PGC) expression (P=0.0004). High PGC expression group showed poor OS than low PGC expression group. (B) Disease-free survival (DFS) for PGC expression (P<0.0001). High PGC level group showed poor DFS than low PGC expression group.

Table 2 Univariate and multivariate analysis of prognostic factors for overall survival and disease-free survival

Prognostic factors	Univariate analysis		Multivariate analysis
	HR (95% CI)	P-value	HR (95% CI)	P-value
Overall survival
PGC expression (high vs low)	3.193 (1.621–6.289)	0.001	3.044 (1.538–6.024)	0.001
Tumor size (cm, <5 vs ≥5)	2.453 (1.297–4.638)	0.006	2.302 (1.211–4.379)	0.011
Gender (male vs female)	1.404 (0.623–3.164)	0.413	–	N.A.
Age (year, <55 vs ≥55)	1.020 (0.993–1.049)	0.144	–	N.A.
HBsAg (negative vs positive)	0.640 (0.296–1.384)	0.256	–	N.A.
ALT (U/L, ≤40 vs >40)	1.484 (0.803–2.740)	0.207	–	N.A.
AFP (ng/mL, ≤20 vs >20)	1.028 (0.533–1.981)	0.934	–	N.A.
Cirrhosis (negative vs positive)	0.638 (0.268–1.520)	0.310	–	N.A.
Tumor number (solitary vs multiple)	1.697 (0.834–3.456)	0.145	–	N.A.
Encapsulation (incomplete vs complete)	0.855 (0.467–1.567)	0.613	–	N.A.
Differentiation (I–II vs III–IV)	0.973 (0.511–1.851)	0.933	–	N.A.
Disease-free survival
PGC expression (high vs low)	3.842 (1.948–7.577)	0.000102	3.955 (1.991–7.858)	0.000086
Tumor size (cm, <5 vs ≥5)	2.604 (1.379–4.918)	0.003	2.687 (1.410–5.120)	0.003
Gender (male vs female)	1.429 (0.634–3.221)	0.389	–	N.A.
Age (year, <55 vs ≥55)	1.015 (0.989–1.042)	0.255	–	N.A.
HBsAg (negative vs positive)	0.656 (0.303–1.422)	0.286	–	N.A.
ALT (U/L, ≤40 vs >40)	1.678 (0.907–3.103)	0.099	–	N.A.
AFP (ng/mL, ≤20 vs >20)	1.156 (0.601–2.224)	0.665	–	N.A.
Cirrhosis (negative vs positive)	0.844 (0.355–2.005)	0.701	–	N.A.
Tumor number (solitary vs multiple)	1.660 (0.814–3.384)	0.163	–	N.A.
Encapsulation (incomplete vs complete)	1.008 (0.550–1.847)	0.979	–	N.A.
Differentiation (I–II vs III–IV)	1.094 (0.575–2.079)	0.785	–	N.A.

Note: Bold values represent  statistical significance.

Abbreviations: N.A., not applicable; PGC, pepsinogen C.

Figure 3 Kaplan–Meier survival curves according to PGC expression in 75 pairs of HCC and adjacent non-tumor tissues stratified by different tumor size. (A) Overall survival (OS) for PGC expression in patients with large tumor size (≥5 cm) or small tumor size (<5 cm). High PGC expression group showed poor OS than low PGC expression group for large tumor size subgroup (red vs green, P=0.0051); while no significant difference was observed in OS between high PGC expression and low PGC expression group for small tumor size subgroup (yellow vs black, P=0.0842). (B) Disease-free survival (DFS) for PGC expression in patients with large tumor size (≥5 cm) or small tumor size (<5 cm). High PGC level group showed poor DFS than low PGC expression group for large tumor size subgroup (red vs green, P=0.0001); while no significant differences were observed in DFS between high PGC level and low-level group for small tumor size subgroup (yellow vs black, P=0.0660).

Figure S1 The subgroup analysis of gender and PGC expression level (OS and DFS) using Kaplan–Meier test. (A) The overall survival rate: for the male subgroup, the high PGC level group showed poor OS than the low-level group (red vs green, P=0.0153); meanwhile, for the female subgroup, the similar statistically significant differences were observed in high and low PGC level (yellow vs black, P=0.0002). (B) The disease-free survival rate: for the male subgroup, the high PGC level group showed poor DFS than the low-level group (red vs green, P=0.0031); likewise, for the female subgroup, the similar statistically significant differences were observed in high and low PGC level (yellow vs black, P=0.0016). Red line: male + high PGC level, n=35; green line: male + low PGC, n=27; yellow line: female <5 cm + high PGC, n=0; black line: female, n=3.