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Int J Biol Sci 2018; 14(10):1333-1342. doi:10.7150/ijbs.26045

Research Paper

Expression of VEGFR-3 in intrahepatic cholangiocarcinoma correlates with unfavorable prognosis through lymphangiogenesis

Meng Sha*, Seogsong Jeong*, Xiao-song Chen*, Ying Tong, Jie Cao, Han-yong Sun, Lei Xia, Ning Xu, Xin Wang, Long-zhi Han, Zhi-feng Xi, Jian-jun Zhang, Xiao-ni Kong, Qiang Xia

Department of Liver Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 1630 Dongfang Road, Shanghai, 200127, China
*Equal contributors: Meng Sha, Seosong Jeong, Xiao-song Chen

Abstract

Background & aims: VEGFR-3 has been shown of great significance in lymph node metastasis and some malignancies, however, its expression in tumors and impact on outcome of intrahepatic cholangiocarcinoma (iCCA) remains unknown. The aim of this study was to assess the role of VEGFR-3 positive tumors for prognosis of iCCA and tumor-associated lymphangiogenesis.

Methods: Clinicopathological features, prognostic factors and survival rate were analyzed to evaluate the influence of VEGFR-3 positive expression on prognosis of iCCA. In addition, tumor-associated lymphangiogenesis quantified as micro-lymphatic vessel density (MLVD) was assessed to explore the correlation between VEGFR-3 expression and lymph node metastasis for iCCA.

Results: Patients with VEGFR-3 positive tumors had increased lymph node metastasis (p=0.025) and were more likely to suffer from tumor recurrence compared with VEGFR-3 negative tumors (p<0.001). VEGFR-3 expression in tumors was identified as an independent prognostic factor for both overall and recurrence-free survival in surgical resected patients with iCCA. In addition, higher MLVD was significantly associated with VEGFR-3 positive expression in tumors (p<0.001), which facilitate lymph node metastasis and significantly worse survival rates.

Conclusions: Our study reveals that VEGFR-3 positive expression in tumors represents an independent prognostic factor for both overall and recurrence-free survival in hepatic resected patients with iCCA. VEGFR-3 positive tumors favor lymph node metastasis, tumor recurrence and worse outcomes through tumor-associated lymphangiogenesis.

Keywords: VEGFR-3 expression, intrahepatic cholangiocarcinoma, lymph node metastasis, tumor-associated lymphangiogenesis, prognosis

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.
How to cite this article:
Sha M, Jeong S, Chen Xs, Tong Y, Cao J, Sun Hy, Xia L, Xu N, Wang X, Han Lz, Xi Zf, Zhang Jj, Kong Xn, Xia Q. Expression of VEGFR-3 in intrahepatic cholangiocarcinoma correlates with unfavorable prognosis through lymphangiogenesis. Int J Biol Sci 2018; 14(10):1333-1342. doi:10.7150/ijbs.26045. Available from http://www.ijbs.com/v14p1333.htm