Clinical Research Papers:

Peritumoral Neuropilin-1 and VEGF receptor-2 expression increases time to recurrence in hepatocellular carcinoma patients undergoing curative hepatectomy

Peng-Yuan Zhuang _, Jian-Dong Wang, Zhao-Hui Tang, Xue-Ping Zhou, Yong Yang, Zhi-Wei Quan, Ying-Bin Liu and Jun Shen

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Oncotarget. 2014; 5:11121-11132. https://doi.org/10.18632/oncotarget.2553

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Peng-Yuan Zhuang1, Jian-Dong Wang1, Zhao-Hui Tang1, Xue-Ping Zhou1, Yong Yang1, Zhi-Wei Quan1, Ying-Bin Liu1, Jun Shen1

1Department of General Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200082, China

Correspondence to:

Jun Shen, e-mail: [email protected]

Keywords: Neuropilin-1, vascular endothelial growth factor receptor-2, peritumoral tissue, overall survival, recurrence

Received: August 04, 2014     Accepted: September 30, 2014     Published: October 11, 2014


Purpose: To determined Neuropilin-1 (NRP-1) and vascular endothelial growth factor receptor 2 (VEGFR-2) expression in the tumoral and peritumoral tissues of 214 treatment-naïve HCC patients and its correlation with overall survival (OS) and time to recurrence (TTR).

Experimental Design: NRP-1 and VEGFR-2 expression were examined by tissue microarray and peritumoral hypoxia by pimonidazole staining and angiogenesis by microvessel density (MVD). OS and TTR were evaluated by Kaplan-Meier analysis and log-rank test.

Results: Peritumoral NRP-1 and VEGFR-2 expression were significantly higher than that of the tumoral tissue (p < 0.001 for both), and high peritumoral expression of both factors was negatively associated with tumor size (p < 0.001 for both). Patients with high peritumoral expression of both proteins had the longest median OS (>94.0 months) and TTR (>84.0 months). The multivariate Cox proportional hazards analysis revealed that patients with high peritumoral expression of both NRP-1 and VEGFR-2 were more than 4 times less likely to have recurrence (p = 0.004) and more than 10 times likely to survive (p < 0.001).

Conclusions: Peritumoral NRP-1 and VEGFR-2 expression is associated with prolonged TTR and extended OS of HCC patients and both may be useful as predictors of surgical outcome of HCC patients and explored as potential therapeutic targets.

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