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Erschienen in: Tumor Biology 3/2014

01.03.2014 | Research Article

Prognostic value of vascular endothelial growth factor A expression in gastric cancer: a meta-analysis

Erschienen in: Tumor Biology | Ausgabe 3/2014

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Abstract

Vascular endothelial growth factor A (VEGF-A) is considered as a prime mediator of angiogenesis and has been implicated in carcinogenesis and metastasis. Various studies examined the relationship between VEGF-A overexpression with the clinical outcome in patients with gastric cancer, but yielded conflicting results. Electronic databases updated to September 2013 were searched to find relevant studies. A meta-analysis was conducted with eligible studies which quantitatively evaluated the relationship between VEGF-A overexpression and survival of patients with gastric cancer. Survival data were aggregated and quantitatively analyzed. We performed a meta-analysis of 20 studies that evaluated the correlation between VEGF-A overexpression and survival in patients with gastric cancer. Combined hazard ratios suggested that VEGF-A overexpression had an unfavorable impact on overall survival (OS) (hazard ratio [HR] = 1.57; 95 % confidence interval [CI], 1.30–1.84) and disease-free survival (DFS) (HR = 1.85; 95 % CI, 1.39–2.32) in patients with gastric cancer. No significant heterogeneity (P = 0.487) was observed among 16 studies for OS and among 7 studies for DFS (P = 0.435). VEGF-A overexpression indicates a poor prognosis for overall survival and disease-free survival in patients with gastric cancer.
Literatur
1.
Zurück zum Zitat Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. Cancer J Clin. 2005;55:74–108.CrossRef Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. Cancer J Clin. 2005;55:74–108.CrossRef
2.
Zurück zum Zitat Amioka T, Kitadai Y, Tanaka S. Vascular endothelial growth factor C expression predicts lymph node metastasis of human gastric carcinoma invading the submucosa. Eur J Cancer. 2002;38:1413–9.PubMedCrossRef Amioka T, Kitadai Y, Tanaka S. Vascular endothelial growth factor C expression predicts lymph node metastasis of human gastric carcinoma invading the submucosa. Eur J Cancer. 2002;38:1413–9.PubMedCrossRef
3.
Zurück zum Zitat Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastrooesophageal junction cancer (ToGA): a phase 3, open-label, randomized controlled trial. Lancet. 2010;376:687–97.PubMedCrossRef Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastrooesophageal junction cancer (ToGA): a phase 3, open-label, randomized controlled trial. Lancet. 2010;376:687–97.PubMedCrossRef
8.
Zurück zum Zitat Zhan P, Wang Q, Qian Q, Yu LK. Risk of venous thromboembolism with the erythropoiesis-stimulating agents (ESAs) for the treatment of cancer-associated anemia: a meta-analysis of randomized control trials. Chin Clin Oncol. 2013. doi:10.3978/j.issn.2304-3865.2013.01.02. Zhan P, Wang Q, Qian Q, Yu LK. Risk of venous thromboembolism with the erythropoiesis-stimulating agents (ESAs) for the treatment of cancer-associated anemia: a meta-analysis of randomized control trials. Chin Clin Oncol. 2013. doi:10.​3978/​j.​issn.​2304-3865.​2013.​01.​02.
11.
Zurück zum Zitat Parmar MK, Torri V, Stewart L. Extracting summary statistics to perform metaanalyses of the published literature for survival endpoints. Stat Med. 1998;17:2815–34.PubMedCrossRef Parmar MK, Torri V, Stewart L. Extracting summary statistics to perform metaanalyses of the published literature for survival endpoints. Stat Med. 1998;17:2815–34.PubMedCrossRef
12.
Zurück zum Zitat Yusuf S, Peto R, Lewis J, et al. Blockade during and after myocardial infarction: an overview of the randomized trials. Prog Cardiovasc Dis. 1985;27:335–71.PubMedCrossRef Yusuf S, Peto R, Lewis J, et al. Blockade during and after myocardial infarction: an overview of the randomized trials. Prog Cardiovasc Dis. 1985;27:335–71.PubMedCrossRef
13.
Zurück zum Zitat DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7:177–88.PubMedCrossRef DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7:177–88.PubMedCrossRef
15.
Zurück zum Zitat Begg CB, Mazumdar M. Operating characteristics of a rank correlation test for publication bias. Biometrics. 1994;50:1088–101.PubMedCrossRef Begg CB, Mazumdar M. Operating characteristics of a rank correlation test for publication bias. Biometrics. 1994;50:1088–101.PubMedCrossRef
16.
Zurück zum Zitat Chen J, Zhou SJ, Zhang Y, Zhang GQ, Zha TZ, Feng YZ et al (2013) Clinicopathological and prognostic significance of galectin-1 and vascular endothelial growth factor expression in gastric cancer. World J Gastroenterol 19(13):2073-9PubMedCentralPubMedCrossRef Chen J, Zhou SJ, Zhang Y, Zhang GQ, Zha TZ, Feng YZ et al (2013) Clinicopathological and prognostic significance of galectin-1 and vascular endothelial growth factor expression in gastric cancer. World J Gastroenterol 19(13):2073-9PubMedCentralPubMedCrossRef
17.
Zurück zum Zitat Yang Q, Ye ZY, Zhang JX, Tao HQ, Li SG, Zhao ZS. Expression of matrix metalloproteinase-9 mRNA and vascular endothelial growth factor protein in gastric carcinoma and its relationship to its pathological features and prognosis. Anat Rec (Hoboken). 2010;293(12):2012–9.CrossRef Yang Q, Ye ZY, Zhang JX, Tao HQ, Li SG, Zhao ZS. Expression of matrix metalloproteinase-9 mRNA and vascular endothelial growth factor protein in gastric carcinoma and its relationship to its pathological features and prognosis. Anat Rec (Hoboken). 2010;293(12):2012–9.CrossRef
18.
Zurück zum Zitat Urano N, Fujiwara Y, Doki Y, Tsujie M, Yamamoto H, Miyata H, et al. Overexpression of hypoxia-inducible factor-1 alpha in gastric adenocarcinoma. Gastric Cancer. 2006;9(1):44–9.PubMedCrossRef Urano N, Fujiwara Y, Doki Y, Tsujie M, Yamamoto H, Miyata H, et al. Overexpression of hypoxia-inducible factor-1 alpha in gastric adenocarcinoma. Gastric Cancer. 2006;9(1):44–9.PubMedCrossRef
19.
Zurück zum Zitat Liu YF, Guo S, Zhao R, Chen YG, Wang XQ, Xu KS (2011) Correlation of vascular endothelial growth factor expression with tumor recurrence and poor prognosis in patients with pN0 gastric cancer. World J Surg 36(1):109-17 Liu YF, Guo S, Zhao R, Chen YG, Wang XQ, Xu KS (2011) Correlation of vascular endothelial growth factor expression with tumor recurrence and poor prognosis in patients with pN0 gastric cancer. World J Surg 36(1):109-17
20.
Zurück zum Zitat Wang XL, Fang JP, Tang RY, Chen XM. Different significance between intratumoral and peritumoral lymphatic vessel density in gastric cancer: a retrospective study of 123 cases. BMC Cancer. 2010;10:299.PubMedCentralPubMedCrossRef Wang XL, Fang JP, Tang RY, Chen XM. Different significance between intratumoral and peritumoral lymphatic vessel density in gastric cancer: a retrospective study of 123 cases. BMC Cancer. 2010;10:299.PubMedCentralPubMedCrossRef
21.
Zurück zum Zitat Wang X, Cao W, Mo M, Wang W, Wu H, Wang J. VEGF and cortactin expression are independent predictors of tumor recurrence following curative resection of gastric cancer. J Surg Oncol. 2010;102(4):325–30.PubMedCrossRef Wang X, Cao W, Mo M, Wang W, Wu H, Wang J. VEGF and cortactin expression are independent predictors of tumor recurrence following curative resection of gastric cancer. J Surg Oncol. 2010;102(4):325–30.PubMedCrossRef
22.
Zurück zum Zitat Lee SJ, Kim JG, Sohn SK, Chae YS, Moon JH, Kim SN, et al. No association of vascular endothelial growth factor-A (VEGF-A) and VEGF-C expression with survival in patients with gastric cancer. Cancer Res Treat. 2009;41(4):218–23.PubMedCentralPubMedCrossRef Lee SJ, Kim JG, Sohn SK, Chae YS, Moon JH, Kim SN, et al. No association of vascular endothelial growth factor-A (VEGF-A) and VEGF-C expression with survival in patients with gastric cancer. Cancer Res Treat. 2009;41(4):218–23.PubMedCentralPubMedCrossRef
23.
Zurück zum Zitat Vidal O, Soriano-Izquierdo A, Pera M, Elizalde JI, Palacin A, Castells A, et al. Positive VEGF immunostaining independently predicts poor prognosis in curatively resected gastric cancer patients: results of a study assessing a panel of angiogenic markers. J Gastrointest Surg. 2008;12(6):1005–14.PubMedCrossRef Vidal O, Soriano-Izquierdo A, Pera M, Elizalde JI, Palacin A, Castells A, et al. Positive VEGF immunostaining independently predicts poor prognosis in curatively resected gastric cancer patients: results of a study assessing a panel of angiogenic markers. J Gastrointest Surg. 2008;12(6):1005–14.PubMedCrossRef
24.
Zurück zum Zitat Lieto E, Ferraraccio F, Orditura M, Castellano P, Mura AL, Pinto M, et al. Expression of vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) is an independent prognostic indicator of worse outcome in gastric cancer patients. Ann Surg Oncol. 2008;15(1):69–79.PubMedCrossRef Lieto E, Ferraraccio F, Orditura M, Castellano P, Mura AL, Pinto M, et al. Expression of vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) is an independent prognostic indicator of worse outcome in gastric cancer patients. Ann Surg Oncol. 2008;15(1):69–79.PubMedCrossRef
25.
Zurück zum Zitat Kolev Y, Uetake H, Takagi Y, Sugihara K. Lactate dehydrogenase-5 (LDH-5) expression in human gastric cancer: association with hypoxia-inducible factor (HIF-1alpha) pathway, angiogenic factors production and poor prognosis. Ann Surg Oncol. 2008;15(8):2336–44.PubMedCrossRef Kolev Y, Uetake H, Takagi Y, Sugihara K. Lactate dehydrogenase-5 (LDH-5) expression in human gastric cancer: association with hypoxia-inducible factor (HIF-1alpha) pathway, angiogenic factors production and poor prognosis. Ann Surg Oncol. 2008;15(8):2336–44.PubMedCrossRef
26.
Zurück zum Zitat Bazas VM, Lukyanova NY, Demash DV, Galakhin KO, Myasoedov DV. Relation between cell-to-cell adhesion and angiogenesis and clinico-morphological prognostic factors in patients with gastric cancer. Exp Oncol. 2008;30(3):235–9.PubMed Bazas VM, Lukyanova NY, Demash DV, Galakhin KO, Myasoedov DV. Relation between cell-to-cell adhesion and angiogenesis and clinico-morphological prognostic factors in patients with gastric cancer. Exp Oncol. 2008;30(3):235–9.PubMed
27.
Zurück zum Zitat Saito H, Osaki T, Murakami D, Sakamoto T, Kanaji S, Ohro S, et al. Prediction of sites of recurrence in gastric carcinoma using immunohistochemical parameters. J Surg Oncol. 2007;95(2):123–8.PubMedCrossRef Saito H, Osaki T, Murakami D, Sakamoto T, Kanaji S, Ohro S, et al. Prediction of sites of recurrence in gastric carcinoma using immunohistochemical parameters. J Surg Oncol. 2007;95(2):123–8.PubMedCrossRef
28.
Zurück zum Zitat Nikiteas NI, Tzanakis N, Theodoropoulos G, Atsaves V, Christoni Z, Karakitsos P, et al. Vascular endothelial growth factor and endoglin (CD-105) in gastric cancer. Gastric Cancer. 2007;10(1):12–7.PubMedCrossRef Nikiteas NI, Tzanakis N, Theodoropoulos G, Atsaves V, Christoni Z, Karakitsos P, et al. Vascular endothelial growth factor and endoglin (CD-105) in gastric cancer. Gastric Cancer. 2007;10(1):12–7.PubMedCrossRef
29.
Zurück zum Zitat Gong W, Wang L, Yao JC, Ajani JA, Wei D, Aldape KD, et al. Expression of activated signal transducer and activator of transcription 3 predicts expression of vascular endothelial growth factor in and angiogenic phenotype of human gastric cancer. Clin Cancer Res. 2005;11(4):1386–93.PubMedCrossRef Gong W, Wang L, Yao JC, Ajani JA, Wei D, Aldape KD, et al. Expression of activated signal transducer and activator of transcription 3 predicts expression of vascular endothelial growth factor in and angiogenic phenotype of human gastric cancer. Clin Cancer Res. 2005;11(4):1386–93.PubMedCrossRef
30.
Zurück zum Zitat Fondevila C, Metges JP, Fuster J, Grau JJ, Palacin A, Castells A, et al. p53 and VEGF expression are independent predictors of tumour recurrence and survival following curative resection of gastric cancer. Br J Cancer. 2004;90(1):206–15.PubMedCentralPubMedCrossRef Fondevila C, Metges JP, Fuster J, Grau JJ, Palacin A, Castells A, et al. p53 and VEGF expression are independent predictors of tumour recurrence and survival following curative resection of gastric cancer. Br J Cancer. 2004;90(1):206–15.PubMedCentralPubMedCrossRef
31.
Zurück zum Zitat Shi H, Xu JM, Hu NZ, Xie HJ. Prognostic significance of expression of cyclooxygenase-2 and vascular endothelial growth factor in human gastric carcinoma. World J Gastroenterol. 2003;9(7):1421–6.PubMed Shi H, Xu JM, Hu NZ, Xie HJ. Prognostic significance of expression of cyclooxygenase-2 and vascular endothelial growth factor in human gastric carcinoma. World J Gastroenterol. 2003;9(7):1421–6.PubMed
32.
Zurück zum Zitat Kaneko T, Konno H, Baba M, Tanaka T, Nakamura S. Urokinase-type plasminogen activator expression correlates with tumor angiogenesis and poor outcome in gastric cancer. Cancer Sci. 2003;94(1):43–9.PubMedCrossRef Kaneko T, Konno H, Baba M, Tanaka T, Nakamura S. Urokinase-type plasminogen activator expression correlates with tumor angiogenesis and poor outcome in gastric cancer. Cancer Sci. 2003;94(1):43–9.PubMedCrossRef
33.
Zurück zum Zitat Yonemura Y, Endo Y, Fujita H, Fushida S, Ninomiya I, Bandou E, et al. Role of vascular endothelial growth factor C expression in the development of lymph node metastasis in gastric cancer. Clin Cancer Res. 1999;5(7):1823–9.PubMed Yonemura Y, Endo Y, Fujita H, Fushida S, Ninomiya I, Bandou E, et al. Role of vascular endothelial growth factor C expression in the development of lymph node metastasis in gastric cancer. Clin Cancer Res. 1999;5(7):1823–9.PubMed
34.
Zurück zum Zitat Maeda K, Kang SM, Onoda N, Ogawa M, Kato Y, Sawada T, et al. Vascular endothelial growth factor expression in preoperative biopsy specimens correlates with disease recurrence in patients with early gastric carcinoma. Cancer. 1999;86(4):566–71.PubMedCrossRef Maeda K, Kang SM, Onoda N, Ogawa M, Kato Y, Sawada T, et al. Vascular endothelial growth factor expression in preoperative biopsy specimens correlates with disease recurrence in patients with early gastric carcinoma. Cancer. 1999;86(4):566–71.PubMedCrossRef
35.
Zurück zum Zitat Tanigawa N, Amaya H, Matsumura M, Shimomatsuya T. Correlation between expression of vascular endothelial growth factor and tumor vascularity, and patient outcome in human gastric carcinoma. J Clin Oncol. 1997;15(2):826–32.PubMed Tanigawa N, Amaya H, Matsumura M, Shimomatsuya T. Correlation between expression of vascular endothelial growth factor and tumor vascularity, and patient outcome in human gastric carcinoma. J Clin Oncol. 1997;15(2):826–32.PubMed
36.
Zurück zum Zitat Parikh AA, Ellis LM. The vascular endothelial growth factor family and its receptors. Hematol Oncol Clin North Am. 2004;18(5):951–71. vii.PubMedCrossRef Parikh AA, Ellis LM. The vascular endothelial growth factor family and its receptors. Hematol Oncol Clin North Am. 2004;18(5):951–71. vii.PubMedCrossRef
37.
Zurück zum Zitat Xie K, Wei D, Shi Q, Huang S. Constitutive and inducible expression and regulation of vascular endothelial growth factor. Cytokine Growth Factor Rev. 2004;15(5):297–324.PubMedCrossRef Xie K, Wei D, Shi Q, Huang S. Constitutive and inducible expression and regulation of vascular endothelial growth factor. Cytokine Growth Factor Rev. 2004;15(5):297–324.PubMedCrossRef
38.
Zurück zum Zitat Hicklin DJ, Ellis LM. Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis. J Clin Oncol. 2005;23(5):1011–27.PubMedCrossRef Hicklin DJ, Ellis LM. Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis. J Clin Oncol. 2005;23(5):1011–27.PubMedCrossRef
39.
Zurück zum Zitat Lee J, Gray A, Yuan J, Luoh SM, Avraham H, Wood WI. Vascular endothelial growth factor-related protein: a ligand and specific activator of the tyrosine kinase receptor Flt4. Proc Natl Acad Sci U S A. 1996;93(5):1988–92.PubMedCentralPubMedCrossRef Lee J, Gray A, Yuan J, Luoh SM, Avraham H, Wood WI. Vascular endothelial growth factor-related protein: a ligand and specific activator of the tyrosine kinase receptor Flt4. Proc Natl Acad Sci U S A. 1996;93(5):1988–92.PubMedCentralPubMedCrossRef
40.
Zurück zum Zitat Jeltsch M, Kaipainen A, Joukov V, Meng X, Lakso M, Rauvala H, et al. Hyperplasia of lymphatic vessels in VEGF-C transgenic mice. Science. 1997;276(5317):1423–5.PubMedCrossRef Jeltsch M, Kaipainen A, Joukov V, Meng X, Lakso M, Rauvala H, et al. Hyperplasia of lymphatic vessels in VEGF-C transgenic mice. Science. 1997;276(5317):1423–5.PubMedCrossRef
41.
Zurück zum Zitat Peng L, Zhan P, Zhou Y, Fang W, Zhao P, Zheng Y, et al. Prognostic significance of vascular endothelial growth factor immunohistochemical expression in gastric cancer: a meta-analysis. Mol Biol Rep. 2012 Oct;39(10):9473–84. Peng L, Zhan P, Zhou Y, Fang W, Zhao P, Zheng Y, et al. Prognostic significance of vascular endothelial growth factor immunohistochemical expression in gastric cancer: a meta-analysis. Mol Biol Rep. 2012 Oct;39(10):9473–84.
42.
Zurück zum Zitat Kyzas PA, Cunha IW, Ioannidis JP. Prognostic significance of vascular endothelial growth factor immunohistochemical expression in head and neck squamous cell carcinoma: a meta-analysis. Clin Cancer Res. 2005;11(4):1434–40.PubMedCrossRef Kyzas PA, Cunha IW, Ioannidis JP. Prognostic significance of vascular endothelial growth factor immunohistochemical expression in head and neck squamous cell carcinoma: a meta-analysis. Clin Cancer Res. 2005;11(4):1434–40.PubMedCrossRef
43.
Zurück zum Zitat Zhan P, Wang J, Lv XJ, Wang Q, Qiu LX, Lin XQ, et al. Prognostic value of vascular endothelial growth factor expression in patients with lung cancer: a systematic review with meta-analysis. J Thorac Oncol. 2009;4(9):1094–103.PubMedCrossRef Zhan P, Wang J, Lv XJ, Wang Q, Qiu LX, Lin XQ, et al. Prognostic value of vascular endothelial growth factor expression in patients with lung cancer: a systematic review with meta-analysis. J Thorac Oncol. 2009;4(9):1094–103.PubMedCrossRef
44.
Zurück zum Zitat Des Guetz G, Uzzan B, Nicolas P, Cucherat M, Morere JF, Benamouzig R, et al. Microvessel density and VEGF expression are prognostic factors in colorectal cancer. Meta-analysis of the literature. Br J Cancer. 2006;94(12):1823–32.PubMedCentralPubMedCrossRef Des Guetz G, Uzzan B, Nicolas P, Cucherat M, Morere JF, Benamouzig R, et al. Microvessel density and VEGF expression are prognostic factors in colorectal cancer. Meta-analysis of the literature. Br J Cancer. 2006;94(12):1823–32.PubMedCentralPubMedCrossRef
45.
Zurück zum Zitat Schoenleber SJ, Kurtz DM, Talwalkar JA, Roberts LR, Gores GJ. Prognostic role of vascular endothelial growth factor in hepatocellular carcinoma: systematic review and meta-analysis. Br J Cancer. 2009;100(9):1385–92.PubMedCentralPubMedCrossRef Schoenleber SJ, Kurtz DM, Talwalkar JA, Roberts LR, Gores GJ. Prognostic role of vascular endothelial growth factor in hepatocellular carcinoma: systematic review and meta-analysis. Br J Cancer. 2009;100(9):1385–92.PubMedCentralPubMedCrossRef
46.
Zurück zum Zitat Kowanetz M, Ferrara N. Vascular endothelial growth factor signaling pathways: therapeutic perspective. Clin Cancer Res. 2006;12(17):5018–22.PubMedCrossRef Kowanetz M, Ferrara N. Vascular endothelial growth factor signaling pathways: therapeutic perspective. Clin Cancer Res. 2006;12(17):5018–22.PubMedCrossRef
47.
Zurück zum Zitat Ferrara N, Hillan KJ, Gerber HP, Novotny W. Discovery and development of bevacizumab, an anti-VEGF antibody for treating cancer. Nat Rev Drug Discov. 2004;3(5):391–400.PubMedCrossRef Ferrara N, Hillan KJ, Gerber HP, Novotny W. Discovery and development of bevacizumab, an anti-VEGF antibody for treating cancer. Nat Rev Drug Discov. 2004;3(5):391–400.PubMedCrossRef
48.
Zurück zum Zitat Begg CB, Berlin JA. Publication bias: a problem in interpreting medical data. J R Stat Soc A. 1988;151:419–63.CrossRef Begg CB, Berlin JA. Publication bias: a problem in interpreting medical data. J R Stat Soc A. 1988;151:419–63.CrossRef
Metadaten
Titel
Prognostic value of vascular endothelial growth factor A expression in gastric cancer: a meta-analysis
Publikationsdatum
01.03.2014
Erschienen in
Tumor Biology / Ausgabe 3/2014
Print ISSN: 1010-4283
Elektronische ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-013-1371-1

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