Gastroenterology Research, ISSN 1918-2805 print, 1918-2813 online, Open Access
Article copyright, the authors; Journal compilation copyright, Gastroenterol Res and Elmer Press Inc
Journal website http://www.gastrores.org

Original Article

Volume 12, Number 2, April 2019, pages 78-87


Prognostic Implications of Arginase and Cytokeratin 19 Expression in Hepatocellular Carcinoma After Curative Hepatectomy: Correlation With Recurrence-Free Survival

Figures

Figure 1.
Figure 1. Expression of arginase-1 and CK19 in HCC. (a) High arginase-1 expression (× 200). (b) Low arginase-1 expression (× 200). (c) Arginase-1 is highly expressed in adjacent benign liver (× 12.5). (d) Positive CK19 expression (× 200). (e) Negative CK19 expression (× 200). (f) CK19 expression in adjacent benign bile duct epithelium (× 200). CK19: cytokeratin 19; HCC: hepatocellular carcinoma.
Figure 2.
Figure 2. Prognostic significance of arginase-1 and CK19. Comparisons of recurrence-free survival and overall survival by CK19 (a, b), arginase-1 (c, d), and arginase-1/CK19 (e, f). CK19: cytokeratin 19.

Tables

Table 1. Associations of Arginase-1/CK19 Expression and Clinicopathologic Parameters in HCC
 
VariablesnArginase-1CK19
HighLowP valuePositiveNegativeP value
HCC: hepatocellular carcinoma; n: number; HBV: hepatitis B virus; HCV: hepatitis C virus; TNM: tumor-node-metastasis; AFP: alpha-fetoprotein; CK19: cytokeratin 19.
Age0.6170.617
  ≥ 655746111146
  < 6555478847
Sex0.160.779
  Male8170111368
  Female31238625
HBV0.0220.103
  Present20200614
  Absent9273191379
HCV10.615
  Present615110952
  Absent514291041
AFP0.2170.083
  Low62548755
  High5039111238
Cirrhosis0.6021
  Present7261111260
  Absent40328733
Tumor size
  ≥ 5 cm292180.0895241
  < 5 cm8372111469
Tumor number0.290.598
  Solitary7363101162
  Multiple39309831
Grade0.3090.077
  I-II685414860
  III-IV443951133
Vascular invasion0.0440.273
  Present30219723
  Absent8272101270
TNM stage0.0091
  I-II9583121679
  III-IV17107314

 

Table 2. Univariate Predictors for RFS and OS in Patients With HCC
 
VariablesnRFSOS
HR95% CIP valueHR95% CIP value
HCC: hepatocellular carcinoma; OS: overall survival; RFS: recurrence-free survival; HR: hazard ratio; CI: confidence interval; HBV: hepatitis B virus; HCV: hepatitis C virus; VI: vascular invasion; TN: tumor number; TNM: tumor-node-metastasis; AFP: alpha-fetoprotein; Arg-1: arginase-1; CK19: cytokeratin 19.
Age0.8160.371
  ≥ 65571.0790.786 - 0.571.5340.594 - 3.96
  < 657611
Sex0.5620.517
  Male811.2440.587 - 2.6371.4280.47 - 4.34
  Female3111
HBV0.2580.905
  Yes201.5730.74 - 3.3460.9280.2686 - 3.207
  No9211
HCV0.0650.273
  Yes610.5430.283 - 1.0430.5940.233 - 1.512
  No5111
AFP0.0040.009
  High502.6391.341 - 5.1943.6171.288 - 10.15
  Low6211
Cirrhosis0.0520.446
  Yes720.5240.275 - 0.9990.6940.275 - 1.759
  No4011
Tumor size0.2820.200
  ≥ 5 cm291.4710.741 - 2.9191.8930.733 - 4.339
  < 5 cm8311
TN0.9390.884
  Multiple391.0270.974 - 0.5230.930.349 - 2.48
  Solitary7311
VI0.00010.0007
  Yes303.6751.906 - 7.0885.1421.987 - 13.31
  No8211
Grade0.000080.0002
  I-II6811
  III-IV443.6941.897 - 7.1966.5382.145 - 19.93
TNM stage0.0010.01
  I-II9511
  III-IV173.5471.765 - 7.1293.5741.378 - 9.265
Arginase0.1850.142
  High931.9040.675 - 5.3693.4890.464 - 26.23
  Low1911
CK190.00020.945
  Positive194.0932.059 - 8.1361.030.277 - 3.308
  Negative9311
Arg-1/CK190.000080.963
  High/positive174.712.31 - 9.1621.3420.298 - 3.56
  Others9511
Arg-1/CK19/TN0.020.884
  High/positive/multiple73.5561.371 - 9.2210.930.349 - 2.479
  Others10511
Arg-1/CK19/TNM stage0.010.242
  High/positive/III/IV74.8150.687 - 13.742.7060.62 - 11.805
  Others10511
Arg-1/CK19/VI0.000080.082
  High/positive/present58.0613.449 - 18.8413.51.033 - 12.36
  Others10711
Arg-1/TNM stage0.020.028
  High932.8810.99 - 8.3826.0910.778 - 47.7
  Low1911
Arg-1/stage III-IV0.030.272
  High104.3940.925 - 20.872.930.343 - 25.167
  Low711
CK19/stage III-IV0.3380.972
  Positive31.8470.55 - 6.1910.9620.111 - 8.322
  Negative1411
Arg-1/VI0.040.072
  High213.0720.881 - 10.7054.6590.595 - 36.4
  Low911
CK19/VI0.0070.744
  Positive74.2951.591 - 11.5941.2530.330 - 4.747
  Negative1211

 

Table 3. Multivariate Predictors for RFS and OS in Patients With HCC
 
VariablesRFSOS
HR95% CIP valueHR95% CIP value
HCC: hepatocellular carcinoma; OS: overall survival; RFS, recurrence-free survival; HR: hazard ratio; CI: confidence interval; TNM: tumor-node-metastasis; AFP: alpha-fetoprotein; CK19: cytokeratin 19. *This P value was obtained from replacement of single variable CK19 to the combined variable in the Cox regression analysis.
AFP1.6290.6130.75060.212.2560.6777.5120.05856
Tumor grade2.7441.24026.0720.015.94321.706620.6960.00512
Vascular invasion1.4560.5813.6460.4221.55370.43255.5820.49947
TNM stage III/IV1.8480.81724.1780.141.4950.47214.7340.49414
CK193.6261.7287.6080.0030.44190.1221.6010.21372
Arginase-1/CK193.1251.51496.4470.002*0.45110.12411.6390.22655*