Genomes and Genes
Gene Symbol: VEGF-C
Description: vascular endothelial growth factor C
Alias: Flt4-L, LMPH1D, VRP, vascular endothelial growth factor C, FLT4 ligand DHM, vascular endothelial growth factor-related protein
- Masood R, Kundra A, Zhu S, Xia G, Scalia P, Smith D, et al. Malignant mesothelioma growth inhibition by agents that target the VEGF and VEGF-C autocrine loops. Int J Cancer. 2003;104:603-10 pubmed..These results indicate that targeting VEGF and VEGF-C simultaneously may be an effective therapeutic approach for malignant mesothelioma. ..
- Tsai P, Shiah S, Lin M, Wu C, Kuo M. Up-regulation of vascular endothelial growth factor C in breast cancer cells by heregulin-beta 1. A critical role of p38/nuclear factor-kappa B signaling pathway. J Biol Chem. 2003;278:5750-9 pubmedb>Vascular endothelial growth factor C (VEGF-C) is a critical activator of tumor lymphangiogenesis that recently has been strongly implicated in the tumor metastasis process...
- Inamine M, Nagai Y, Mitsuhashi A, Nagase S, Yaegashi N, Yoshikawa H, et al. Cigarette smoke stimulates VEGF-C expression in cervical intraepithelial neoplasia (CIN) 1 and 2 lesions. Int J Clin Oncol. 2012;17:498-504 pubmed publisher..No significant difference was observed among the HPV risk groups in both average Ki-67 and VEGF-C expression. These findings suggest that VEGF-C may play an important role in cigarette smoking-associated cervical carcinogenesis. ..
- Cho H, Kim I, Park S, Baek K, Nam I, Park S, et al. VEGF-C mediates RhoGDI2-induced gastric cancer cell metastasis and cisplatin resistance. Int J Cancer. 2014;135:1553-63 pubmed publisher..Our results indicate that RhoGDI2 might be a potential therapeutic target for simultaneously reducing metastasis risk and enhancing chemotherapy efficacy in gastric cancer. ..
- Liu P, Zhou J, Zhu H, Xie L, Wang F, Liu B, et al. VEGF-C promotes the development of esophageal cancer via regulating CNTN-1 expression. Cytokine. 2011;55:8-17 pubmed publisherb>Vascular endothelial growth factor C (VEGF-C) is a key regulator of angiogenesis and lymphangiogenesis. VEGF-C is also implicated in the development of esophageal cancer...
- He M, Cheng Y, Li W, Liu Q, Liu J, Huang J, et al. Vascular endothelial growth factor C promotes cervical cancer metastasis via up-regulation and activation of RhoA/ROCK-2/moesin cascade. BMC Cancer. 2010;10:170 pubmed publisherThe elevated expression of vascular endothelial growth factor C (VEGF-C) is correlated with clinical cervical cancer metastasis and patient survival, which is interpreted by VEGF-C functions to stimulate angiogenesis and lymphatic genesis...
- Kumar B, Chile S, Ray K, Reddy G, Addepalli M, Kumar A, et al. VEGF-C differentially regulates VEGF-A expression in ocular and cancer cells; promotes angiogenesis via RhoA mediated pathway. Angiogenesis. 2011;14:371-80 pubmed publisher..Further, knockdown studies of RhoA even with supplementation of VEGF-C or A has resulted in decreased endothelial cell proliferation and stress fiber formation, indicating that VEGF-C does promote angiogenesis via RhoA mediated pathway. ..
- Khromova N, Kopnin P, Rybko V, Kopnin B. Downregulation of VEGF-C expression in lung and colon cancer cells decelerates tumor growth and inhibits metastasis via multiple mechanisms. Oncogene. 2012;31:1389-97 pubmed publisher..These results are consistent with the idea of high potentiality of VEGF-C as a cancer drug target. ..
- Saintigny P, Kambouchner M, Ly M, Gomes N, Sainte Catherine O, Vassy R, et al. Vascular endothelial growth factor-C and its receptor VEGFR-3 in non-small-cell lung cancer: concurrent expression in cancer cells from primary tumour and metastatic lymph node. Lung Cancer. 2007;58:205-13 pubmed..As VEGF-C/VEGFR-3 coexpression is very frequent in metastatic LN tumour cells, it can be hypothesised that this coexpression participates in the growth of LN metastasis. ..
- Chien M, Liu Y, Hsin C, Lin C, Shih C, Yang S, et al. Impact of VEGF-C gene polymorphisms and environmental factors on oral cancer susceptibility in Taiwan. PLoS ONE. 2013;8:e60283 pubmed publisher..Gene-environmental interactions among VEGF-C polymorphisms, smoking, and betel-quid chewing might alter one's susceptibility to oral cancer. ..
- Leppänen V, Tvorogov D, Kisko K, Prota A, Jeltsch M, Anisimov A, et al. Structural and mechanistic insights into VEGF receptor 3 ligand binding and activation. Proc Natl Acad Sci U S A. 2013;110:12960-5 pubmed publisher..Taken together, our data show that ligand-dependent homotypic interactions in D5 and D7 are essential for VEGFR activation, opening promising possibilities for the design of VEGFR-specific drugs. ..
- Matsumura S, Oue N, Mitani Y, Kitadai Y, Yasui W. DNA demethylation of vascular endothelial growth factor-C is associated with gene expression and its possible involvement of lymphangiogenesis in gastric cancer. Int J Cancer. 2007;120:1689-95 pubmed..0001). These results suggest that demethylation and activation of the VEGF-C gene is likely involved in lymphangiogenesis in GC. ..
- Timoshenko A, Chakraborty C, Wagner G, Lala P. COX-2-mediated stimulation of the lymphangiogenic factor VEGF-C in human breast cancer. Br J Cancer. 2006;94:1154-63 pubmed..These results, for the first time, demonstrate a regulatory role of COX-2 in VEGF-C synthesis (and thereby lymphangiogenesis) in human breast cancer, which is mediated at least in part by EP1/EP4 receptors. ..
- Karkkainen M, Haiko P, Sainio K, Partanen J, Taipale J, Petrova T, et al. Vascular endothelial growth factor C is required for sprouting of the first lymphatic vessels from embryonic veins. Nat Immunol. 2004;5:74-80 pubmed..Defects in lymphatic vessel formation or function cause lymphedema. Here we show that the vascular endothelial growth factor C (VEGF-C) is required for the initial steps in lymphatic development...
- Dias S, Choy M, Alitalo K, Rafii S. Vascular endothelial growth factor (VEGF)-C signaling through FLT-4 (VEGFR-3) mediates leukemic cell proliferation, survival, and resistance to chemotherapy. Blood. 2002;99:2179-84 pubmed..These results identify the VEGF-C/FLT-4 pathway as a novel therapeutic target for the treatment of subsets of acute leukemia. ..
- Su J, Shih J, Yen M, Jeng Y, Chang C, Hsieh C, et al. Cyclooxygenase-2 induces EP1- and HER-2/Neu-dependent vascular endothelial growth factor-C up-regulation: a novel mechanism of lymphangiogenesis in lung adenocarcinoma. Cancer Res. 2004;64:554-64 pubmed..Taken together, our results provided evidence that COX-2 up-regulated VEGF-C and promotes lymphangiogenesis in human lung adenocarcinoma via the EP(1)/Src/HER-2/Neu signaling pathway. ..
- Nakazato T, Shingaki S, Kitamura N, Saito C, Kuwano R, Tachibana M. Expression level of vascular endothelial growth factor-C and -A in cultured human oral squamous cell carcinoma correlates respectively with lymphatic metastasis and angiogenesis when transplanted into nude mouse oral cavity. Oncol Rep. 2006;15:825-30 pubmed..Since VEGF-C is a lymphangiogenic factor, these results suggest that expression of VEGF-C is a useful predictor for LN metastasis. ..
- Nakashima T, Kondoh S, Kitoh H, Ozawa H, Okita S, Harada T, et al. Vascular endothelial growth factor-C expression in human gallbladder cancer and its relationship to lymph node metastasis. Int J Mol Med. 2003;11:33-9 pubmedLymph node metastasis is a major prognostic factor in human cancer. Vascular endothelial growth factor C (VEGF-C) is a lymphangiogenic polypeptide that has been implicated in several human solid tumors...
- Hong J, Kim T, Kim H, Park E, Yang E, Kim S. Genetic association of angiogenesis- and hypoxia-related gene polymorphisms with osteonecrosis of the femoral head. Exp Mol Med. 2010;42:376-85 pubmed..0018-0.0037, OR>3). Collectively, our findings suggest that genetic variations in angiogenesis- and hypoxia-related genes may help to identify susceptibility factors for the development of ONFH in the Korean population. ..
- Sinn B, Darb Esfahani S, Wirtz R, Faggad A, Weichert W, Buckendahl A, et al. Vascular endothelial growth factor C mRNA expression is a prognostic factor in epithelial ovarian cancer as detected by kinetic RT-PCR in formalin-fixed paraffin-embedded tissue. Virchows Arch. 2009;455:461-7 pubmed publisherb>Vascular endothelial growth factor C (VEGF-C) is a well described chemotactic and growth factor for lymphatic endothelial cells. Its inhibition leads to suppression of lymphatic and distant metastases in mouse models...
- Matsuura M, Onimaru M, Yonemitsu Y, Suzuki H, Nakano T, Ishibashi H, et al. Autocrine loop between vascular endothelial growth factor (VEGF)-C and VEGF receptor-3 positively regulates tumor-associated lymphangiogenesis in oral squamoid cancer cells. Am J Pathol. 2009;175:1709-21 pubmed publisher..These findings together suggested that the VEGF-C/FLT-4 autocrine loop in tumor cells was a potential enhancer system to promote cancer progression, and FLT-4 in tumor tissue might become an effective target for cancer therapy. ..
- Shin H, Smith M, Toy K, Williams P, Bizios R, Gerritsen M. VEGF-C mediates cyclic pressure-induced endothelial cell proliferation. Physiol Genomics. 2002;11:245-51 pubmed..Cyclic pressure is, therefore, a mechanical force that modulates endothelial cell functions (such as proliferation) by activating a specific transcriptional program. ..
- Schoppmann S, Birner P, Stockl J, Kalt R, Ullrich R, Caucig C, et al. Tumor-associated macrophages express lymphatic endothelial growth factors and are related to peritumoral lymphangiogenesis. Am J Pathol. 2002;161:947-56 pubmed..In conclusion VEGF-C-expressing TAMs play a novel role in peritumoral lymphangiogenesis and subsequent dissemination in human cancer. ..
- 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;41:217-22 pubmed..COX-2 and VEGF-C may play an important role in tumor progression by stimulating lymphangiogenesis. The inhibition of lymphangiogenesis, COX-2, or VEGF-C activity may have an important therapeutic benefit in the control of NSCLC. ..
- Witte D, Thomas A, Ali N, Carlson N, Younes M. Expression of the vascular endothelial growth factor receptor-3 (VEGFR-3) and its ligand VEGF-C in human colorectal adenocarcinoma. Anticancer Res. 2002;22:1463-6 pubmed..05), but not with lymph node metastasis or depth of tumor invasion. Our results suggest that VEGFs promote cancer growth not only by stimulating angiogenesis, but also by acting on receptors present on the cancer cells themselves. ..
- Feng L, Zheng X, Zhou L, Fu B, Yu Y, Lu S, et al. Correlation between expression of S100A4 and VEGF-C, and lymph node metastasis and prognosis in gastric carcinoma. J Int Med Res. 2011;39:1333-43 pubmedThis semiquantitative immunohistochemical study investigated the clinical significance of S100A4 and vascular endothelial growth factor C (VEGF-C) protein expression in gastric carcinoma...
- Gu Y, Qi X, Guo S. Lymphangiogenesis induced by VEGF-C and VEGF-D promotes metastasis and a poor outcome in breast carcinoma: a retrospective study of 61 cases. Clin Exp Metastasis. 2008;25:717-25 pubmed publisher..LVD may serve as a predictor of lymph node metastasis and a prognostic factor in breast carcinoma. VEGF-C and VEGF-D play an important role in lymphangiogenesis making the carcinoma more aggressive and leading to a poor prognosis. ..
- Byeon J, Jung H, Lee Y, Lee D, Lee G, Myung S, et al. Clinicopathological significance of vascular endothelial growth factor-C and cyclooxygenase-2 in esophageal squamous cell carcinoma. J Gastroenterol Hepatol. 2004;19:648-54 pubmed..Thus the investigation of VEGF-C expression in ESCC may assist in management planning. ..
- Kigure W, Fujii T, Sutoh T, Morita H, Katoh T, Yajima R, et al. The association of VEGF-C expression with tumor lymphatic vessel density and lymph node metastasis in patients with gastric cancer and gastrointestinal stromal tumor. Hepatogastroenterology. 2013;60:277-80 pubmed publisher..The clinical observation that GIST rarely metastasizes to the lymph nodes may depend on the lack of VEGF-C expression. ..
- Ueda M, Terai Y, Yamashita Y, Kumagai K, Ueki K, Yamaguchi H, et al. Correlation between vascular endothelial growth factor-C expression and invasion phenotype in cervical carcinomas. Int J Cancer. 2002;98:335-43 pubmed..0132) and VEGF-C tissue status emerged as an independent prognostic parameter (p = 0.0232). These results suggest that VEGF-C expression is closely related to invasion phenotype and affects the patient's survival in cervical carcinomas. ..
- Li D, Xie K, Ding G, Li J, Chen K, Li H, et al. Tumor resistance to anti-VEGF therapy through up-regulation of VEGF-C expression. Cancer Lett. 2014;346:45-52 pubmed publisher..Our findings indicate that tumors may develop resistance to anti-VEGF therapy by activating the VEGF-C pathway. ..
- Joukov V, Sorsa T, Kumar V, Jeltsch M, Claesson Welsh L, Cao Y, et al. Proteolytic processing regulates receptor specificity and activity of VEGF-C. EMBO J. 1997;16:3898-911 pubmedThe recently identified vascular endothelial growth factor C (VEGF-C) belongs to the platelet-derived growth factor (PDGF)/VEGF family of growth factors and is a ligand for the endothelial-specific receptor tyrosine kinases VEGFR-3 and ..
- Chen Y, Jiang L, She F, Tang N, Wang X, Li X, et al. Vascular endothelial growth factor-C promotes the growth and invasion of gallbladder cancer via an autocrine mechanism. Mol Cell Biochem. 2010;345:77-89 pubmed publisher..In conclusion, GBC cells express both VEGF-C and its receptors. VEGF-C may have a role in the progressive growth and invasion of human GBC through an autocrine mechanism...
- Huang K, Sui L. The relevance and role of vascular endothelial growth factor C, matrix metalloproteinase-2 and E-cadherin in epithelial ovarian cancer. Med Oncol. 2012;29:318-23 pubmed publisherWe investigated the correlation of vascular endothelial growth factor C, matrix metalloproteinase-2, E-cadherin to explore mechanisms of vascular endothelial growth factor C in the metastasis of ovarian cancer and the relationship of ..
- Su J, Yang P, Shih J, Yang C, Wei L, Hsieh C, et al. The VEGF-C/Flt-4 axis promotes invasion and metastasis of cancer cells. Cancer Cell. 2006;9:209-23 pubmed..The VEGF-C/Flt-4 axis, through upregulation of contactin-1, may regulate the invasive capacity in different types of cancer cells. ..
- Zheng S, Huang R, Zhang Y. [Role of matrix metalloproteinase (MMP)-2 and -9 and vascular endothelial growth factor C in lymph node metastasis of breast cancer]. Zhonghua Bing Li Xue Za Zhi. 2010;39:240-4 pubmed..The expression of MMP-2, MMP-9 and VEGF-C in MCF-7 cells after gene transfection decreased significantly (P < 0.05). MMP-2 and MMP-9 in conjunction with VEGF-C, promote lymphangiogenesis and lymph node metastasis of breast cancer. ..
- Tanaka T, Ishiguro H, Kuwabara Y, Kimura M, Mitsui A, Katada T, et al. 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 pubmed publisher..In addition, the indication of non-surgical therapy is gaining more attention. Vascular endothelial growth factor C (VEGF-C) is potentially lymphangiogenic and selectively induces hyperplasia of the lymphatic ..
- Joukov V, Pajusola K, Kaipainen A, Chilov D, Lahtinen I, Kukk E, et al. 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;15:1751 pubmed
- Simiantonaki N, Jayasinghe C, Michel Schmidt R, Peters K, Hermanns M, Kirkpatrick C. Hypoxia-induced epithelial VEGF-C/VEGFR-3 upregulation in carcinoma cell lines. Int J Oncol. 2008;32:585-92 pubmed..Our findings suggest that under hypoxic conditions an autocrine loop between VEGF-C/VEGFR-3 and HIF-1 alpha is possible in breast carcinoma and lung carcinoma but not in colorectal carcinoma cell lines. ..
- Foster R, Satchell S, Seckley J, Emmett M, Joory K, Xing C, et al. VEGF-C promotes survival in podocytes. Am J Physiol Renal Physiol. 2006;291:F196-207 pubmed..Together, these results suggest for the first time that VEGF-C acts in an autocrine manner in cultured podocytes to promote survival, although the receptor or receptor complex activated has yet to be elucidated. ..
- Kyzas P, Stefanou D, Agnantis N. COX-2 expression correlates with VEGF-C and lymph node metastases in patients with head and neck squamous cell carcinoma. Mod Pathol. 2005;18:153-60 pubmed..Also, the predictive ability for mortality of regional lymph node metastasis can be improved with the combined evaluation of the immunohistochemical expression of these two proteins. ..
- Jennbacken K, Vallbo C, Wang W, Damber J. Expression of vascular endothelial growth factor C (VEGF-C) and VEGF receptor-3 in human prostate cancer is associated with regional lymph node metastasis. Prostate. 2005;65:110-6 pubmedb>Vascular endothelial growth factor C (VEGF-C) and its receptor, VEGFR-3, have been implicated as important factors in the formation of lymphatic vessels and recent evidence suggests that tumor lymphangiogenesis promotes lymphatic ..
- Kurahara H, Takao S, Maemura K, Shinchi H, Natsugoe S, Aikou T. Impact of vascular endothelial growth factor-C and -D expression in human pancreatic cancer: its relationship to lymph node metastasis. Clin Cancer Res. 2004;10:8413-20 pubmed..017). VEGF-C and -D expression in tumor cells in the marginal portion of the tumor significantly associated with lymphatic metastasis and prognosis in patients with pancreatic head cancer. ..
- Tuomi L, Johansson M, Lindell E, Folkestad L, Malmerfors M, Finizia C. Voice Range Profile and Health-related Quality of Life Measurements Following Voice Rehabilitation After Radiotherapy; a Randomized Controlled Study. J Voice. 2017;31:115.e9-115.e16 pubmed publisher..b>VRP area demonstrated a statistically significant difference when comparing changes over time, where the study group ..
- Li G, Yang F, Gu S, Li Z, Xue M. MicroRNA-101 induces apoptosis in cisplatin-resistant gastric cancer cells by targeting VEGF-C. Mol Med Rep. 2016;13:572-8 pubmed publisher..In conclusion, the results of the present study suggested that miRâ€‘101 inhibited the proliferation and promoted DDPâ€‘induced apoptosis of DDPâ€‘resistant gastric cancer cells, at least in part via targeting VEGF-C. ..
- Yao L, Testini C, Tvorogov D, Anisimov A, Vargas S, Baluk P, et al. Pulmonary lymphangiectasia resulting from vascular endothelial growth factor-C overexpression during a critical period. Circ Res. 2014;114:806-22 pubmed publisher..The findings indicate that VEGF-C overexpression can induce pulmonary lymphangiectasia during a critical period in perinatal development. ..
- Xu Q, Sun T, Tian H, Wang C, Zhou H. Ultrasound-mediated vascular endothelial growth factor C (VEGF-C) gene microbubble transfection inhibits growth of MCF-7 breast cancer cells. Oncol Res. 2013;20:297-301 pubmed..The present study highlights that VEGF-C siRNA in combination with ultrasound-mediated microbubble destruction (UMMD) could be a powerful, promising nonviral technology for breast cancer gene therapy. ..
- Kondo K, Kaneko T, Baba M, Konno H. VEGF-C and VEGF-A synergistically enhance lymph node metastasis of gastric cancer. Biol Pharm Bull. 2007;30:633-7 pubmedb>Vascular endothelial growth factor C (VEGF-C) is the most important molecule in lymphangiogenesis and its relationship with lymph node metastasis has attracted considerable interest...
- Yamaguchi T, Fushida S, Yamamoto Y, Tsukada T, Kinoshita J, Oyama K, et al. Tumor-associated macrophages of the M2 phenotype contribute to progression in gastric cancer with peritoneal dissemination. Gastric Cancer. 2016;19:1052-1065 pubmed publisher..Therefore, intraperitoneal TAMs are expected to be a promising target in the treatment of peritoneal dissemination in gastric cancer. ..
- Zuo S, Ji Y, Wang J, Guo J. Expression and clinical implication of HIF-1alpha and VEGF-C in non-small cell lung cancer. J Huazhong Univ Sci Technolog Med Sci. 2008;28:674-6 pubmed publisher..HIF-1alpha and VEGF-C were over-expressed in NSCLC. They may be involved in the carcinogenesis of NSCLC, and play an important role in invasion and metastasis of NSCLC. HIF-1alpha and VEGF-C work synergically in the process of NSCLC. ..
- Marton I, Knezevic F, Ramic S, Milosevic M, Tomas D. Immunohistochemical expression and prognostic significance of HIF-1? and VEGF-C in neuroendocrine breast cancer. Anticancer Res. 2012;32:5227-32 pubmed..Moreover, patients with NEBC exhibiting moderate or strong VEGF-C expression could be candidates for a specific VEGF-C antibody therapy. ..
- Cai X, Ma S, Gu M, Zu C, Qu W, Zheng X. Survivin regulates the expression of VEGF-C in lymphatic metastasis of breast cancer. Diagn Pathol. 2012;7:52 pubmed publisher..The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/9193530897100952. ..
- Jiang M, Gou H, Yang Y, Cao D, Hou M. [Relationship between clinicopathologic characteristics and expression of VEGF-C and VEGF-D in esophageal squamous cancer]. Sichuan Da Xue Xue Bao Yi Xue Ban. 2009;40:240-4 pubmed..691, P < 0.001). VEGF-C and VEGF-D might promote lymphatic metastasis by inducing lymphangiogenesis especially at the edge of esophageal squamous carcinoma tissue. ..
- Sahutoglu T, Sakaci T, Hasbal N, Ahbap E, Kara E, Sumerkan M, et al. Serum VEGF-C levels as a candidate biomarker of hypervolemia in chronic kidney disease. Medicine (Baltimore). 2017;96:e6543 pubmed publisher..The lack of correlation between VEGF-C and EF may hold a promise to eliminate this common confounder. Further studies are needed to define the clinical utility of VEGF-C in volume management. ..
- DeMei M, XiangXin L, YongPing X, YongXia Y, YunHai Y, Lin Z. Vascular endothelial growth factor C expression is closely correlated with lymph node recurrence and poor prognosis in patients with early stage cervical cancer. J Int Med Res. 2013;41:1541-9 pubmed publisher..These findings indicate that detection of VEGF-C mRNA has clinical potential as a predictor for identifying patients with pN0 cervical cancer at high risk of lymph node recurrence and poor prognosis. ..
- Kono M, Watanabe M, Abukawa H, Hasegawa O, Satomi T, Chikazu D. Cyclo-oxygenase-2 expression is associated with vascular endothelial growth factor C expression and lymph node metastasis in oral squamous cell carcinoma. J Oral Maxillofac Surg. 2013;71:1694-702 pubmed publisher..Recently, cyclo-oxygenase-2 (COX-2) level has been found to correlate highly with vascular endothelial growth factor C (VEGF-C) and lymph node metastasis, as in other solid tumors...
- Xiang Z, Zeng Z, Tang Z, Fan J, Sun H, Wu W, et al. [Nuclear accumulation of CXCR4 and overexpressions of VEGF-C and CK19 are associated with a higher risk of lymph node metastasis in hepatocellular carcinoma]. Zhonghua Zhong Liu Za Zhi. 2010;32:344-9 pubmed..Increased protein expressions of nuclear CXCR4, VEGF-C, and CK-19 are independent risk factors for developing lymph node metastasis, and they are significantly correlated with LNM and poor outcome in HCC patients. ..