Vascular Endothelial Growth Factor C is an Indicator of Lymph Node Metastasis in Thoracic Esophageal Squamous Cellcarcinomas and Its Role in Long-term Survival After Surgery

Overview

Journal Thorac Cancer

Specialties Oncology
Pulmonary Medicine

Date 2016 Jan 15

PMID 26767018

Citations 1

Authors

Xufeng Pan

Teng Mao

Wentao Fang

Wenhu Chen

Affiliations

Soon will be listed here.

Abstract

Background: To define the role of vascular endothelial growth factor C (VEGF-C) on lymph node (LN) metastasis of human esophageal squamous cell carcinoma (ESCC), and to investigate its impact on overall survival.

Methods: Real-time polymerase chain reaction was introduced to quantify the expression of VEGF-CmRNA. One hundred and eight samples (59 tumor tissue and 59 paired normal tissue) were analyzed.

Results: VEGF-CmRNA expression was significantly higher in tumor tissues than in normal mucosa (P = 0.02). VEGF-CmRNA expression was significantly higher in LN (+) patients than in LN (-) patients (P = 0.04). VEGF-CmRNA expression was related to a positive LN number (P = 0.06) and a positive LN station number (P = 0.04). VEGF-CmRNA expression was significantly higher in stage III and IV patients than in stage I and II patients (P = 0.03). A logistic regression model showed that VEGF-CmRNA and T status were independent risk factors for LN metastasis(P < 0.05). In univariate analysis, survival tended to be poorer in the VEGF-CmRNA high expression group (22.0 months vs. 44.0 months, P = 0.08). A Cox regression model revealed that a positive LN station number was the only independent risk factor for overall survival (P < 0.01).

Conclusion: VEGF-C was a useful indicator for LN metastasis in human ESCC, and it might have some influence on long-term survival by affecting LN metastasis.

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References

Tanaka T, Ishiguro H, Kuwabara Y, Kimura M, Mitsui A, Katada T . Vascular endothelial growth factor C (VEGF-C) in esophageal cancer correlates with lymph node metastasis and poor patient prognosis. J Exp Clin Cancer Res. 2010; 29:83. PMC: 2917417. DOI: 10.1186/1756-9966-29-83. View

Li X, Liu B, Xiao J, Yuan Y, Ma J, Zhang Y . Roles of VEGF-C and Smad4 in the lymphangiogenesis, lymphatic metastasis, and prognosis in colon cancer. J Gastrointest Surg. 2011; 15(11):2001-10. DOI: 10.1007/s11605-011-1627-2. View

Liu P, Chen W, Zhu H, Liu B, Song S, Shen W . Expression of VEGF-C correlates with a poor prognosis based on analysis of prognostic factors in 73 patients with esophageal squamous cell carcinomas. Jpn J Clin Oncol. 2009; 39(10):644-50. DOI: 10.1093/jjco/hyp079. View

Yavuz S, Paydas S, Disel U, Zorludemir S, Erdogan S . VEGF-C expression in breast cancer: clinical importance. Adv Ther. 2006; 22(4):368-80. DOI: 10.1007/BF02850084. View

Sundar S, Ganesan T . Role of lymphangiogenesis in cancer. J Clin Oncol. 2007; 25(27):4298-307. DOI: 10.1200/JCO.2006.07.1092. View

Pajusola K, Aprelikova O, Korhonen J, Kaipainen A, Pertovaara L, Alitalo R . FLT4 receptor tyrosine kinase contains seven immunoglobulin-like loops and is expressed in multiple human tissues and cell lines. Cancer Res. 1992; 52(20):5738-43. View

Guo X, Chen Y, Xu Z, Xu Z, Qian Y, Yu X . Prognostic significance of VEGF-C expression in correlation with COX-2, lymphatic microvessel density, and clinicopathologic characteristics in human non-small cell lung cancer. Acta Biochim Biophys Sin (Shanghai). 2009; 41(3):217-22. DOI: 10.1093/abbs/gmp004. View

Liu P, Zhou J, Zhu H, Xie L, Wang F, Liu B . VEGF-C promotes the development of esophageal cancer via regulating CNTN-1 expression. Cytokine. 2011; 55(1):8-17. DOI: 10.1016/j.cyto.2011.03.008. View

Jeltsch M, Kaipainen A, Joukov V, Meng X, Lakso M, Rauvala H . Hyperplasia of lymphatic vessels in VEGF-C transgenic mice. Science. 1997; 276(5317):1423-5. DOI: 10.1126/science.276.5317.1423. View

10.

Wu Q, She H, Liang J, Huang Y, Yang Q, Yang Q . Expression and clinical significance of extracellular matrix protein 1 and vascular endothelial growth factor-C in lymphatic metastasis of human breast cancer. BMC Cancer. 2012; 12:47. PMC: 3292501. DOI: 10.1186/1471-2407-12-47. View

11.

Bustin S, Benes V, Nolan T, Pfaffl M . Quantitative real-time RT-PCR--a perspective. J Mol Endocrinol. 2005; 34(3):597-601. DOI: 10.1677/jme.1.01755. View

12.

Joukov V, Pajusola K, Kaipainen A, Chilov D, Lahtinen I, Kukk E . A novel vascular endothelial growth factor, VEGF-C, is a ligand for the Flt4 (VEGFR-3) and KDR (VEGFR-2) receptor tyrosine kinases. EMBO J. 1996; 15(2):290-98. PMC: 449944. View

13.

Ye J, Wu X, Wu D, Wu P, Ni C, Zhang Z . miRNA-27b targets vascular endothelial growth factor C to inhibit tumor progression and angiogenesis in colorectal cancer. PLoS One. 2013; 8(4):e60687. PMC: 3625233. DOI: 10.1371/journal.pone.0060687. View

14.

Hoeben A, Landuyt B, Highley M, Wildiers H, van Oosterom A, De Bruijn E . Vascular endothelial growth factor and angiogenesis. Pharmacol Rev. 2004; 56(4):549-80. DOI: 10.1124/pr.56.4.3. View

15.

Liu Y, Ma L, Wang S, Chen Y, Wu G, Han M . Prognostic value of lymph node metastases and lymph node ratio in esophageal squamous cell carcinoma. Eur J Surg Oncol. 2009; 36(2):155-9. DOI: 10.1016/j.ejso.2009.09.005. View

16.

Sun Z, Wang Z, Zhang M . Correlation between vascular endothelial growth factor C expression and prognosis in patients with esophageal squamous cell carcinomas after Ivor-Lewis esophagectomy. Asia Pac J Clin Oncol. 2012; 8(4):e68-76. DOI: 10.1111/j.1743-7563.2011.01514.x. View

17.

Kunisaki C, Shimada H, Akiyama H, Nomura M, Matsuda G, Ono H . Prognostic factors in esophageal cancer. Hepatogastroenterology. 2004; 51(57):736-40. View

18.

Ferlay J, Shin H, Bray F, Forman D, Mathers C, Parkin D . Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2011; 127(12):2893-917. DOI: 10.1002/ijc.25516. View

19.

Paavonen K, Horelli-Kuitunen N, Chilov D, Kukk E, Pennanen S, Kallioniemi O . Novel human vascular endothelial growth factor genes VEGF-B and VEGF-C localize to chromosomes 11q13 and 4q34, respectively. Circulation. 1996; 93(6):1079-82. DOI: 10.1161/01.cir.93.6.1079. View

20.

Gao P, Zhou G, Zhang Q, Su Z, Zhang T, Xiang L . Lymphangiogenesis in gastric carcinoma correlates with prognosis. J Pathol. 2009; 218(2):192-200. DOI: 10.1002/path.2523. View