Carcinogenesis Carcinogenesis Advance Access published August 2, 2014
Stem cell factor is a novel independent prognostic biomarker for hepatocellular carcinoma after curative resection
Carcinogenesis
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Manuscript ID: Manuscript Type:
CARCIN-2014-00473.R1
Original Manuscript
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Date Submitted by the Author:
Complete List of Authors:
09-Jul-2014
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hao, jihui; Tianjin Medical University Cancer Institute and Hospital, Department of Pancreatic Cancer Wang, Xiuchao; Tianjin Medical University Cancer Institute and Hospital, Department of Pancreatic Cancer Ren, He; Tianjin Medical University Cancer Institute and Hospital, Department of Pancreatic Cancer Zhao, Tiansuo; Tianjin Medical University Cancer Institute and Hospital, Department of Pancreatic Cancer Jia, Li; Barts Cancer Institute, Queen Mary University of London, Centre for Haemato-Oncology sun, wei; Tianjin Medical University Cancer Institute and Hospital, Department of Pancreatic Cancer chen, jing; Tianjin Medical University Cancer Institute and Hospital, Department of Pancreatic Cancer sun, yan; Tianjin Medical University Cancer Institute and Hospital, Department of Pathology ma, weidong; Tianjin Medical University Cancer Institute and Hospital, Department of Pancreatic Cancer wang, jian; Tianjin Medical University Cancer Institute and Hospital, Department of Pancreatic Cancer gao, chuntao; Tianjin Medical University Cancer Institute and Hospital, Department of Pancreatic Cancer lang, mingxiao; Tianjin Medical University Cancer Institute and Hospital, Department of Pancreatic Cancer Gao, Song; Tianjin Medical University Cancer Institute and Hospital, Department of Pancreatic Cancer
Keywords:
Hepatocellular carcinoma, biomarker, stem cell factor, MVD-CD34
Downloaded from http://carcin.oxfordjournals.org/ at New York University on October 10, 2014
Journal:
Page 1 of 33
Stem cell factor is a novel independent prognostic biomarker for hepatocellular carcinoma after curative resection Xiuchao Wang,1,† He Ren,1, † Tiansuo Zhao,1 Jing Chen,1 Wei Sun,1 Yan Sun,2 Weidong Ma,1 Jian Wang,1 Chuntao Gao,1 Song Gao,1 Mingxiao Lang,1 Li Jia,3 # and Jihui Hao1 #
Department of Abdominal Oncology, 2Department of Pathology, National Clinical Research Center for Cancer, Key Lab of Cancer Treatment and Prevention, Tianjin Medical University Cancer Institute and Hospital, Tianjin, PR China; 3 Centre for Haemato-Oncology, Barts Cancer Institute, Queen Mary University of London, London, United Kingdom
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rP †
These authors contributed equally to this work
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To whom correspondence should be addressed: Jihui Hao, Tel: +86-2223340123-3070, Fax: 862223537796; email [email protected]; and Li Jia, Tel: +44 (0)20 7882 3825, Fax: +44 (0)20 7882 3891; email [email protected]
Downloaded from http://carcin.oxfordjournals.org/ at New York University on October 10, 2014
1
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1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
Carcinogenesis
Carcinogenesis
Abstract Stem cell factor (SCF), a ligand of c-kit, is a hematopoietic growth factor. Uncontrolled activity of SCF/c-kit signaling pathway contributes to the formation of a variety of human malignancies. In this study, we determined whether SCF expression could risk-stratify patients with hepatocellular carcinoma (HCC) after curative resection. HCC tissues from 160 patients were collected during curative resection and stained with SCF and CD34, a marker for microvessel density (MVD), using immunohistochemistry. Two statistical analyses were performed: an independent
Kaplan-Meier estimated outcome measures of overall survival (OS) and relapse-free survival (RFS). We found that higher levels of SCF confer worse OS (continuous P=0.014; and
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categorical P=0.009), and RFS (continuous P=0.002; categorical P=0.003) of patients with HCC. SCF varies independently from MVD-CD34, TNM, histologic grade, age and gender, and retains
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prognostic significance when analyzed as a categorical variable in a multivariate analysis. We confirmed that MVD-CD34 is also an independent prognostic marker for patients with HCC. The
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levels of SCF and CD34 showed a positive and significant correlation (P30.67. P=0.0009 indicates significant separation
Downloaded from http://carcin.oxfordjournals.org/ at New York University on October 10, 2014
were analyzed by the Mann-Whitney U test. (C and D) Kaplan-Meier survival curves of HCC
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1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
Carcinogenesis
Carcinogenesis
amount these groups. (B) Relapse-free survival. Four subgroups were defined according to the cut-off point for both SCF (85%) and CD34 (26.33): SCF 26.33; SCF
HIGH
/CD34
HIGH
LOW
LOW
/CD34
= SCF 85% and CD34
= SCF >85% and CD34 >26.33. P 5cm
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1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
Carcinogenesis
Carcinogenesis
Suppl Table 3. Multivariate analysis for SCF-adjusted risk factors on clinical outcome
OS
RFS P value 0.056 0.004
2.52 (1.53-4.14) 2.05 (1.31-3.20)
Stem cell factor is a novel independent prognostic biomarker for hepatocellular carcinoma after curative resection
Carcinogenesis
Fo
Manuscript ID: Manuscript Type:
CARCIN-2014-00473.R1
Original Manuscript
rP
Date Submitted by the Author:
Complete List of Authors:
09-Jul-2014
w
ie ev
rR
ee
hao, jihui; Tianjin Medical University Cancer Institute and Hospital, Department of Pancreatic Cancer Wang, Xiuchao; Tianjin Medical University Cancer Institute and Hospital, Department of Pancreatic Cancer Ren, He; Tianjin Medical University Cancer Institute and Hospital, Department of Pancreatic Cancer Zhao, Tiansuo; Tianjin Medical University Cancer Institute and Hospital, Department of Pancreatic Cancer Jia, Li; Barts Cancer Institute, Queen Mary University of London, Centre for Haemato-Oncology sun, wei; Tianjin Medical University Cancer Institute and Hospital, Department of Pancreatic Cancer chen, jing; Tianjin Medical University Cancer Institute and Hospital, Department of Pancreatic Cancer sun, yan; Tianjin Medical University Cancer Institute and Hospital, Department of Pathology ma, weidong; Tianjin Medical University Cancer Institute and Hospital, Department of Pancreatic Cancer wang, jian; Tianjin Medical University Cancer Institute and Hospital, Department of Pancreatic Cancer gao, chuntao; Tianjin Medical University Cancer Institute and Hospital, Department of Pancreatic Cancer lang, mingxiao; Tianjin Medical University Cancer Institute and Hospital, Department of Pancreatic Cancer Gao, Song; Tianjin Medical University Cancer Institute and Hospital, Department of Pancreatic Cancer
Keywords:
Hepatocellular carcinoma, biomarker, stem cell factor, MVD-CD34
Downloaded from http://carcin.oxfordjournals.org/ at New York University on October 10, 2014
Journal:
Page 1 of 33
Stem cell factor is a novel independent prognostic biomarker for hepatocellular carcinoma after curative resection Xiuchao Wang,1,† He Ren,1, † Tiansuo Zhao,1 Jing Chen,1 Wei Sun,1 Yan Sun,2 Weidong Ma,1 Jian Wang,1 Chuntao Gao,1 Song Gao,1 Mingxiao Lang,1 Li Jia,3 # and Jihui Hao1 #
Department of Abdominal Oncology, 2Department of Pathology, National Clinical Research Center for Cancer, Key Lab of Cancer Treatment and Prevention, Tianjin Medical University Cancer Institute and Hospital, Tianjin, PR China; 3 Centre for Haemato-Oncology, Barts Cancer Institute, Queen Mary University of London, London, United Kingdom
rR
ee
rP †
These authors contributed equally to this work
w
ie ev
To whom correspondence should be addressed: Jihui Hao, Tel: +86-2223340123-3070, Fax: 862223537796; email [email protected]; and Li Jia, Tel: +44 (0)20 7882 3825, Fax: +44 (0)20 7882 3891; email [email protected]
Downloaded from http://carcin.oxfordjournals.org/ at New York University on October 10, 2014
1
Fo
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
Carcinogenesis
Carcinogenesis
Abstract Stem cell factor (SCF), a ligand of c-kit, is a hematopoietic growth factor. Uncontrolled activity of SCF/c-kit signaling pathway contributes to the formation of a variety of human malignancies. In this study, we determined whether SCF expression could risk-stratify patients with hepatocellular carcinoma (HCC) after curative resection. HCC tissues from 160 patients were collected during curative resection and stained with SCF and CD34, a marker for microvessel density (MVD), using immunohistochemistry. Two statistical analyses were performed: an independent
Kaplan-Meier estimated outcome measures of overall survival (OS) and relapse-free survival (RFS). We found that higher levels of SCF confer worse OS (continuous P=0.014; and
rP
categorical P=0.009), and RFS (continuous P=0.002; categorical P=0.003) of patients with HCC. SCF varies independently from MVD-CD34, TNM, histologic grade, age and gender, and retains
ee
prognostic significance when analyzed as a categorical variable in a multivariate analysis. We confirmed that MVD-CD34 is also an independent prognostic marker for patients with HCC. The
rR
levels of SCF and CD34 showed a positive and significant correlation (P30.67. P=0.0009 indicates significant separation
Downloaded from http://carcin.oxfordjournals.org/ at New York University on October 10, 2014
were analyzed by the Mann-Whitney U test. (C and D) Kaplan-Meier survival curves of HCC
Fo
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
Carcinogenesis
Carcinogenesis
amount these groups. (B) Relapse-free survival. Four subgroups were defined according to the cut-off point for both SCF (85%) and CD34 (26.33): SCF 26.33; SCF
HIGH
/CD34
HIGH
LOW
LOW
/CD34
= SCF 85% and CD34
= SCF >85% and CD34 >26.33. P 5cm
Fo
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
Carcinogenesis
Carcinogenesis
Suppl Table 3. Multivariate analysis for SCF-adjusted risk factors on clinical outcome
OS
RFS P value 0.056 0.004
2.52 (1.53-4.14) 2.05 (1.31-3.20)
