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01-12-2013 | Translational Research and Biomarkers

High Expression of Proline-Rich Tyrosine Kinase2 is Associated with Poor Survival of Hepatocellular Carcinoma via Regulating Phosphatidylinositol 3-Kinase/AKT Pathway

Authors: Jie Cao, MD, Yao Chen, PhD, Jing Fu, PhD, You-Wen Qian, PhD, Yi-Bin Ren, PhD, Bo Su, PhD, Tao Luo, PhD, Rong-Yang Dai, PhD, Liang Huang, MD, Jian-Jun Yan, MD, Meng-Chao Wu, MD, Yi-Qun Yan, MD, Hong-Yang Wang, MD, PhD

Published in: Annals of Surgical Oncology | Special Issue 3/2013

Abstract

Background

The peritumoral environment has been implicated to be important in the process of metastasis and recurrence in hepatocellular carcinoma (HCC). Our aims were to assess the prognostic value of proline-rich tyrosine kinase 2 (Pyk2) in HCC and investigate related molecular mechanism.

Methods

Expression of Pyk2 was tested by immunohistochemistry in tissue microarrays containing 141 paired HCC samples. Correlation between Pyk2 and vascular endothelial growth factor (VEGF) expression in clinical samples was analyzed by Spearman rank correlation. Matrigel invasion, anchorage-independent growth assay and immunoblotting were performed to study the effect of Pyk2 on the invasion and progression of HCC cells and phosphoinositide 3-kinase (PI3K)/AKT pathway activation.

Results

Higher Pyk2 density in both tumor and peritumor was associated with lower overall survival (P = 0.044; P = 0.041, respectively), serum AFP levels > 1,000 ng/ml (P = 0.013; P = 0.032, respectively) and postoperative distant metastasis (both P < 0.001). However, only higher peritumoral Pyk2 density was related to lower disease-free survival (P = 0.014) and vascular invasion (P = 0.035). A significant correlation between Pyk2 and VEGF density in tumor or peritumoral liver tissue was observed (r = 0. 3133, P = 0.0002; r = 0.5176, P < 0.0001, respectively). Immunoblotting showed that Pyk2 activated PI3K–AKT pathway to upregulate VEGF expression in HL-7702, SMMC-7721 and HepG2 cells.

Conclusions

High Pyk2, especially peritumoral Pyk2 was associated with poor survival, disease recurrence, and metastasis in HCC. PI3K-AKT pathway was involved in Pyk2-mediated VEGF expression during HCC progression and invasion.

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Title: High Expression of Proline-Rich Tyrosine Kinase2 is Associated with Poor Survival of Hepatocellular Carcinoma via Regulating Phosphatidylinositol 3-Kinase/AKT Pathway
Authors: Jie Cao, MD
Yao Chen, PhD
Jing Fu, PhD
You-Wen Qian, PhD
Yi-Bin Ren, PhD
Bo Su, PhD
Tao Luo, PhD
Rong-Yang Dai, PhD
Liang Huang, MD
Jian-Jun Yan, MD
Meng-Chao Wu, MD
Yi-Qun Yan, MD
Hong-Yang Wang, MD, PhD
Publication date: 01-12-2013
Publisher: Springer US
Published in: Annals of Surgical Oncology / Issue Special Issue 3/2013
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI: https://doi.org/10.1245/s10434-012-2372-9

Keynote webinar | Spotlight on medication adherence

Springer Medicine

High Expression of Proline-Rich Tyrosine Kinase2 is Associated with Poor Survival of Hepatocellular Carcinoma via Regulating Phosphatidylinositol 3-Kinase/AKT Pathway

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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