Supporting Information

Supporting Table 1. Summary of clinicopathologic variables
Characteristic / Number of patients
Patients / 141
Sex
Male / 124
Female / 17
Age (years) / 22-78, median 50
Virus marker
HBV(+) and HCV(–) / 115
HBV(–) and HCV(+) / 5
HBV(–) and HCV(–) / 19
HBV(+) and HCV(+) / 2
AFP
<20 ng/ml / 34
20-1000 ng/ml / 53
>1000 ng/ml / 54
Tumor size (cm) / 1.2-22, median 6
Liver cirrhosis
Yes / 74
No / 67
Vascular invasion
Yes / 72
No / 69
Intrahepatic metastasis
Yes / 43
No / 98
Capsular formation
Yes / 87
No / 54
TNM stage
I / 104
II / 5
III / 30
IV / 2
Postoperative distant metastasis
Yes / 41
No / 100
Time of follow-up (months) / 1-92, median 36
Abbreviations: HBV(+), hepatitis B surface antigen positive; HCV(+), anti-hepatitis C virus antibody positive; (–), negative; AFP, serum alpha-fetoprotein; TNM, tumor-nodes-metastasis, based on the American Joint Committee on Cancer/International Union Against Cancer staging system(6th edition, 2002).

Supporting Table2. Average density of intratumoral/peritumoral Pyk2 staining

Density

/

Median

/

Q1-Q3

/

Range

/

P*

Pyk2

/ / / /

Intratumoral

/

0.0506

/ 0.0261- 0.1088 / 0.0002- 0.2747 /

Peritumoral

/

0.0563

/

0.0372- 0.0805

/

0.0000- 0.2540

/

0.418

Normal liver

/

0.0005

/

0.0001- 0.0014

/

0.0000- 0.0078

/

0.001

The density of Pyk2 was represented as the index of the integrated optical density/total area (see Patients and Methods for detail).Pyk2, proline-rich tyrosine kinase-2. *Mann–Whitney Utest. Q1: the first quartile; Q3: the third quartile.
Supporting Table.3 Univariate and Multivariate Analyses of Factors Associated With Survival and Recurrence
/

OS

/

DFS

/ Univariate P / Multivariate / Univariate P /

Multivariate

Factor

/ HazardRatio / 95% CI /

P

/ HazardRatio / 95% CI /

P

Sex:female v male

/

0.386

/ / /

NA

/

0.315

/ / /

NA

Year: 50 v > 50 years /

0.408

/ / /

NA

/

0.333

/ / /

NA

Size: 5cmv5cm

/

0.001

/ / /

NS

/

0.001

/ / /

NS

AFP: 20 v > 20 ng/ml

/

0.253

/ / /

NA

/

0.309

/ / /

NA

Vascular invasion: yes v no

/

0.001

/

1.985

/

1.067-3.694

/

0.029

/

0.001

/

1.957

/

1.138-3.365

/

0.006

Intrahepatic metastasis: yes v no

/

0.001

/ / /

NS

/

0.001

/

1.696

/

1.056-2.725

/

0.028

Capsular formation: yes v no

/

0.079

/ / /

NA

/

0.055

/ / /

NS

HBsAg:positive v negative /

0.20

/ / /

NA

/

0.162

/ / /

NA

TNM: Ⅰ-ⅡvⅢ-Ⅳ

/

0.001

/

3.392

/

2.001-5.750

/

<.001

/

0.001

/

2.195

/

1.316-3.660

/

0.001

Edmondson:Ⅰ-ⅡvⅢ-Ⅳ

/

0.270

/ / /

NA

/

0.166

/ / /

NA

Distant metastasis: yes v no

/

0.001

/

5.456

/

3.081-9.657

/

<.001

/

0.001

/

4.831

/

2.853-8.180

/

0.001

IntratumoralPyk2: low v high

/

0.044

/ / /

NS

/

0.081

/ / /

NA

PeritumoralPyk2: low v high

/

0.041

/ / /

NS

/

0.014

/ / /

NS

Abbreviations: OS, overall survival; DFS, disease-free survival; NA, not adopted; NS, not significant;HBsAg, hepatitis B surface antigen; Pyk2, proline-rich tyrosine kinase-2; TNM, tumor-nodes-metastasis.
SupportingTable 4. Relationship between intratumoral/peritumoral p-AKT expression and clinicopathologic features
Characteristics / Intratumoralp-AKT / P / Peritumoral p-AKT / P
low (n = 71) / High (n = 70) / Low (n = 71) / High (n = 70)
Sex / NS / NS
Male / 63 / 61 / 60 / 64
Female / 8 / 9 / 11 / 6
Age (years) / NS / NS
50 / 33 / 40 / 35 / 38
> 50 / 38 / 30 / 36 / 32
Tumor size (cm) / NS / NS
5 / 34 / 26 / 32 / 28
> 5 / 37 / 44 / 39 / 42
AFP
20 ng/ml / 17 / 17 / NS / 17 / 17 / NS
>20 ng/ml / 54 / 53 / 54 / 53
1000 ng/ml / 50 / 37 / 0.032 / 49 / 38 / 0.072
>1000 ng/ml / 21 / 33 / 22 / 32
HBsAg / NS / NS
positive / 59 / 58 / 60 / 57
negative / 12 / 12 / 11 / 13
HCV antibody / NS† / NS†
positive / 3 / 4 / 5 / 2
negative / 68 / 66 / 66 / 68
Liver cirrhosis / NS / NS
Yes / 40 / 35 / 38 / 37
No / 31 / 35 / 33 / 33
Vascular invasion / NS / 0.002
Yes / 31 / 41 / 27 / 45
No / 40 / 29 / 44 / 25
Intrahepatic metastasis / 0.039 / NS
Yes / 16 / 27 / 18 / 25
No / 55 / 43 / 53 / 45
Capsular formation / NS / NS
Yes / 41 / 46 / 47 / 40
No / 30 / 24 / 24 / 30
Postoperative distant metastasis / <0.001 / <0.001
Yes / 10 / 31 / 11 / 30
No / 61 / 39 / 60 / 40
pTNM stage / NS / NS
I-II / 57 / 52 / 56 / 53
III-IV / 14 / 18 / 15 / 17
141 patients with HCC were divided into p-AKT ‘‘High’’ group (whose final intratumoral/peritumoral densitywas higher than the median) and ‘‘Low’’ group (whose final intratumoral/peritumoral density waslower than the median). The patient and disease profiles in each group werecompared.† Fisher’s exact test.NS, not significant.
SupportingTable5. Relationship between intratumoral/peritumoral VEGF expression and clinicopathologic features
Characteristics / Intratumoral VEGF / P / Peritumoral VEGF / P
low (n = 71) / High (n = 70) / Low (n = 71) / High (n = 70)
Sex / NS / NS
Male / 63 / 61 / 62 / 62
Female / 8 / 9 / 9 / 8
Age (years) / NS / NS
50 / 40 / 33 / 37 / 36
> 50 / 31 / 37 / 34 / 34
Tumor size (cm) / NS / NS
5 / 33 / 27 / 30 / 30
> 5 / 38 / 43 / 41 / 40
AFP
20 ng/ml / 14 / 20 / NS / 22 / 12 / 0.055
>20 ng/ml / 57 / 50 / 49 / 58
1000 ng/ml / 45 / 42 / NS / 50 / 37 / 0.032
>1000 ng/ml / 26 / 28 / 21 / 33
HBsAg / 0.067 / NS
positive / 58 / 59 / 59 / 58
negative / 13 / 11 / 12 / 12
HCV antibody / NS† / NS†
positive / 2 / 5 / 3 / 4
negative / 69 / 65 / 68 / 66
Liver cirrhosis / NS / NS
Yes / 37 / 38 / 33 / 42
No / 34 / 32 / 38 / 28
Vascular invasion / NS / 0.015
Yes / 36 / 36 / 29 / 43
No / 35 / 34 / 42 / 27
Intrahepatic metastasis / NS / NS
Yes / 23 / 20 / 21 / 22
No / 48 / 50 / 50 / 48
Capsular formation / NS / NS
Yes / 39 / 48 / 43 / 44
No / 32 / 22 / 28 / 26
Postoperative distant metastasis / 0.036 / <0.001
Yes / 15 / 26 / 10 / 31
No / 56 / 44 / 61 / 39
pTNM stage / NS / NS
I-II / 52 / 57 / 56 / 53
III-IV / 19 / 13 / 15 / 17
141 patients with HCC were divided into VEGF ‘‘High’’ group (whose final intratumoral/peritumoral densitywas higher than the median) and ‘‘Low’’ group (whose final intratumoral/peritumoral density waslower than the median). The patient and disease profiles in each group werecompared.† Fisher’s exact test.NS, not significant.