血管內皮生長因子與食管癌預后相關性的Meta分析_《中國循證醫學雜志》

作者：

王確 , 周儒白 , 田李星 ,  盧鈾

四川大學華西醫院（成都 610041）;

關鍵詞：

食管癌血管內皮生長因子預后生存率 Meta分析隊列研究

DOI：

10.7507/1672-2531.20130098

視頻：

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摘要 全文 圖表 視頻 參考文獻 施引文獻 補充材料

目的　采用Meta分析方法評價血管內皮生長因子（vascular endothelial growth factor，VEGF）在食管癌預后中的價值。
方法　計算機檢索PubMed、EMbase中VEGF與食管癌預后相關性的回顧性隊列研究，并輔以文獻追溯方法查找相關文獻。檢索時限均從建庫至2012年6月。由2名評價者按納入與排除標準獨立選擇文獻、提取資料和評價質量后，采用RevMan 5.0軟件進行Meta分析，并用Begg’s漏斗圖和Egger’s法評估文獻的發表偏倚。
結果　最終納入10個隊列研究，共811例食管癌患者。Meta分析結果顯示，VEGF高表達的食管癌患者死亡風險更高［HR=1.55，95%CI（1.25，1.91）］。進一步按VEGF亞型、VEGF表達臨界值及患者來源進行的亞組分析結果顯示，VEGF-C在組織的高表達與預后并無顯著聯系。臨界值為10%的VEGF亞組在腫瘤組織的高表達提示死亡風險更高，而臨界值為30%的亞組VEGF表達水平與預后并無顯著聯系。中國患者VEGF在腫瘤組織的高表達較非中國患者對預測食管癌預后更具價值。
結論　VEGF在腫瘤組織的表達水平對食管癌的預后具有預測價值。

引用本文： 王確,周儒白,田李星,盧鈾. 血管內皮生長因子與食管癌預后相關性的Meta分析. 中國循證醫學雜志, 2013, 13(5): 553-559. doi: 10.7507/1672-2531.20130098 復制

1.	Bradbury PA, Zhai R, Ma C, et al. Vascular endothelial growth factor polymorphisms and esophageal cancer prognosis. Clin Cancer Res, 2009, 15(14): 4680-4685.
2.	Crew KD, Neugut A. Epidemiology of upper gastrointestinal malignancies. Semin Oncol, 2004, 31(4): 450-464.
3.	蔡燕, 陳先卓, 彭乙華, 等. 食管癌組織中存活蛋白的異常表達. 重慶醫學, 2012, 41(5): 432-434.
4.	Jemal A, Bray F, Center MM, et al. Global cancer statistics. CA Cancer J Clin, 2011, 61(2): 134.
5.	Yoko O, Satoshi Y, Kunihiro Y, et al. Angiogenesis-Related Factors are Molecular Targets for Diagnosis and Treatment of Patients with Esophageal Carcinoma. Ann Thorac CardiovascSurg, 2010, 16(6): 389-393.
6.	Vallböhmer D, Lenz HJ. Predictive and prognostic molecular markers in outcome of esophageal cancer. Diseases of the Esophagus, 2006, 19(6): 425-432.
7.	Ferrara N, Davis-Smyth T. The biology of vascular endothelial growth factor. Endocr Rev, 1997, 18(1): 4-25.
8.	Toi M, Matsumoto T, Bando H, et al. Vascular endothelial growth factor: its prognostic, predictive, and therapeutic implications. Lancet Oncol, 2001, 2(11): 667-673.
9.	Shih CH, Ozawa S, Ando N, et al. Vascular endothelial growth factor expression predicts outcome and lymph node metastasis in squamous cell carcinoma of the esophagus. Clin Cancer Res, 2000, 6(3): 1161-1168.
10.	Kitadai Y, Haruma K, Tokutomi T, et al. Significance of vessel count and vascular endothelial growth factor in human esophageal carcinomas. Clin Cancer Res, 1998, 4(9): 2195-2200.
11.	Inoue K, Ozeki Y, Suganuma T, et al. Vascular endothelial growth factor expression in primary esophageal squamous cell carcinoma. Association with angiogenesis and tumor progression. Cancer, 1997, 79(2): 206-213.
12.	Kleespies A, Guba M, Jauch KW, et al. Vascular endothelial growth factor in esophageal cancer. J SurgOncol, 2004, 87(2): 95-104.
13.	William PT, David PK, David HI, et al. Targeted Therapies for Esophageal Cancer. The Oncologist, 2005, 10(8): 590-601.
14.	李寶江, 賈王生, 臧長運. 食管癌組織VEGF的表達與腫瘤血管生成的關系. 實用癌癥雜志, 2000, 15(6): 583-584.
15.	Poon RTP, Fan ST, Wong J, et al. Clinical significance of angiogenesis in gastrointestinal cancers – a target of novel prognostic and therapeutic approaches. Ann Surg, 2003, 238(1): 9-28.
16.	Nicosia R. What is the role of vascular endothelial growth factorrelated molecules in tumor angiogenesis. Am J Pathol, 1998, 153(1): 11-16.
17.	Miroslaw K, Oksana K, Robert M, et al. Serum vascular endothelial growth factors C and D in patients with oesophageal cancer. Eur J Cardio-thoracic Surg, 2010, 38(3): 260-267.
18.	Cavazzola LT, Rosa AR, Schirmer CC, et al. Immunohistochemical evaluation for P53 and VEGF (Vascular Endothelial Growth Factor) is not prognostic for long term survival in end stage esophageal adenocarcinoma. Rev Col Bras Cir, 2009, 36(1): 24-34.
19.	Koide N, Nishio A, Hiraguri M, et al. Coexpression of vascular endothelial growth factor and p53 protein in squamous cell carcinoma of the esophagus. Am J Gastroenterol, 2001, 96(6): 1733-1740.
20.	Shih CH, Ozawa S, Ando N, et al. Vascular endothelial growth factor expression predicts outcome and lymph node metastasis in squamous cell carcinoma of the esophagus. Clin Cancer Res, 2000, 6(3): 1161-1168.
21.	Rosa AR, Schirmer CC, Gurki RR, et al. Prognostic value of p53 protein expression and vascular endothelial growth factor expression in resected squamous cell carcinoma of theesophagus. Dis Esophagus, 2003, 16(2): 112-118.
22.	Shimada H, Takeda A, Nabeya Y, et al. Clinical significance of serum vascular endothelial growth factor in esophageal squamous cell carcinoma. Cancer, 2001, 92(3): 663-669.
23.	季衛忠, 顧汝軍. 食管癌患者手術治療前后血清IGF-I、VEGF和TSGF檢測的臨床意義. 放射免疫學雜志, 2011, 24(5): 496-497.
24.	Kimura H, Kato H, Tanaka N, et al. Preoperative serum vascular endothelial growth factor-C (VEGF-C) levels predict recurrence in patients with esophageal cancer. Anticancer Res, 2008, 28(1A): 165-169.
25.	Krzystek-Korpacka M, Matusiewicz M, Diakowska D, et al. Up-regulation of VEGF-C secreted by cancer cells and not VEGF-A correlates with clinical evaluation of lymph node metastasis in esophageal squamous cell carcinoma (ESCC). Cancer Lett, 2007, 249(2): 171-177.
26.	Naumnik W, Izycki T, Swidzin´ska E, et al. Serumlevels of VEGF-C, VEGF-D, and sVEGF-R2 in patients with lung cancer during chemotherapy. Oncol Res, 2007, 16(9): 445-451.
27.	Moundhri MS, Shukaili A, Nabhani M, et al. Measurement of circulating levels of VEGF-A, -C, and -D and their receptors, VEGFR-1 and -2 in gastric adenocarcinoma. World J Gastroenterol, 2008, 14(24): 3879-3883.
28.	Des GG, Uzzan B, Nicolas P, et al. Microvessel density and VEGF expression are prognostic factors in colorectal cancer: Meta-analysis of the literature. Br J Cancer, 2006, 94(12): 1823-1832.
29.	Li C, Zang J, Li XS, et al. Prognostic role of vascular endothelial growth factor in oral carcinoma: a meta analysis. West China Journal of Stomatology, 2011, 29(1): 39-43.
30.	Chen J, Li T, Wu Y, et al. Prognostic significance of vascular endothelial growth factor expression in gastric carcinoma: a meta-analysis. J Cancer Res ClinOncol, 2011, 137(12): 1799-1812.
31.	Schoenleber SJ, Kurtz DM, Talwalkar JA, et al. Prognostic role of vascular endothelial growth factor in hepatocellular carcinoma: Systematic review and meta-analysis. Br J Cancer, 2009, 100(9): 1385-1392.
32.	Veikkola T, Alitalo K. VEGFS, receptors and angiogenesis. Semin Cancer Bio, 1999, 9(3): 211-220.
33.	Jeltsch M, Kaipainen A, Joukov V, et al. Hyperplasia of lymphatic vessels in VEGF-Ctransgenicmice. Science, 1997, 277(5325): 463.
34.	Chen M, Cai E, Huang J, et al. Prognostic Value of Vascular Endothelial Growth Factor Expression in Patients with Esophageal Cancer: ASystematic Review and Meta-analysis. Cancer Epidemiol Biomarkers Prev, 2012, 21(7): 1126-1134.
35.	Akemi I, Hiromitsu M, Natsuya K, et al. Intratumorallymphangiogenesis of esophageal squamouscell carcinoma and relationship with regulatory factorsand prognosis. Pathology International, 2008, 58(10): 611-619.
36.	Ching T, Shih CL, Ho J, et al. Expression of hypoxia-inducible factor(HIF)-1α and vascular endothelial growthfactor (VEGF)-D as outcome predictors inresected esophageal squamous cell carcinoma. Disease Markers, 2008, 25(3): 141-148.
37.	Shimada H, Hoshino T, Okazumi S, et al. Expression of angiogenic factors predicts response tochemoradiotherapy and prognosis of oesophageal squamous cellcarcinoma. Br J Cancer, 2002, 86(4): 552-557.
38.	Joon YC, Kee-Taek J, Young MS, et al. Prognostic Significance of Vascular Endothelial GrowthFactor Expression and Microvessel Density in EsophagealSquamous Cell Carcinoma: Comparison With PositronEmission Tomography. Annals of Surgical Oncology, 2006, 13(8): 1054-1062.
39.	Myung J, Se-Jin J, Yong W, et al. Clinical Prognostic Values of Vascular Endothelial Growth Factor,Microvessel Density, and p53 Expression in Esophageal Carcinomas. J Korean Med Sci, 2002, 17(2): 201-207.
40.	Liu P, Chen W, Zhu H, et al. Expression of VEGF-C Correlates with a Poor Prognosis Basedon Analysis of Prognostic Factors in 73 Patients with EsophagealSquamous Cell Carcinomas. Jpn J ClinOncol, 2009, 39(10): 644-650.
41.	Tatsuya T, Hideyuki I, Yoshiyuki K, et al. Vascular endothelial growth factor C and D expression correlates with lymph node metastasis and poor prognosis in patients with resected esophageal cancer. J Experimental Clin Cancer Research, 2010, 29: 83.
42.	Okazawa T, Yoshida T, Shirai Y, et al. Expression of Vascular EndothelialGrowth Factor C is a Prognostic Indicatorin Esophageal Cancer. Hepato-Gastroenterology, 2008, 55(86-87): 1503-1508.
43.	Sun ZG, Wang Z, Liu XY, et al. Mucin 1 and Vascular Endothelial Growth Factor C ExpressionCorrelates with Lymph Node Metastatic Recurrence in Patientswith N0 Esophageal Cancer After Ivor-Lewis Esophagectomy. World J Surg, 2011, 35(1): 70-77.
44.	Kozlowski M, Naumnik W, Niklinski J, et al. Vascular endothelial growth factor C and D expression correlates with lymph node metastasis and poor prognosis in patients with resected esophageal cancer. Neoplasma, 2011, 58(4): 311-319.
45.	Reigetsu Y, Yoshinori F, Kenji K, et al. Cyclooxygenase-2 expression after preoperative chemoradiotherapy correlates with more frequent esophageal cancer recurrence. World J Gastroenterol, 2007, 13(16): 2283-2288.
46.	Lisa MM, Douglas GA, Willi S, et al. Reporting recommendations for tumor MARKer prognostic studies (REMARK). Nature, 2005, 2(8): 416-422.

1. Bradbury PA, Zhai R, Ma C, et al. Vascular endothelial growth factor polymorphisms and esophageal cancer prognosis. Clin Cancer Res, 2009, 15(14): 4680-4685.
2. Crew KD, Neugut A. Epidemiology of upper gastrointestinal malignancies. Semin Oncol, 2004, 31(4): 450-464.
3. 蔡燕, 陳先卓, 彭乙華, 等. 食管癌組織中存活蛋白的異常表達. 重慶醫學, 2012, 41(5): 432-434.
4. Jemal A, Bray F, Center MM, et al. Global cancer statistics. CA Cancer J Clin, 2011, 61(2): 134.
5. Yoko O, Satoshi Y, Kunihiro Y, et al. Angiogenesis-Related Factors are Molecular Targets for Diagnosis and Treatment of Patients with Esophageal Carcinoma. Ann Thorac CardiovascSurg, 2010, 16(6): 389-393.
6. Vallböhmer D, Lenz HJ. Predictive and prognostic molecular markers in outcome of esophageal cancer. Diseases of the Esophagus, 2006, 19(6): 425-432.
7. Ferrara N, Davis-Smyth T. The biology of vascular endothelial growth factor. Endocr Rev, 1997, 18(1): 4-25.
8. Toi M, Matsumoto T, Bando H, et al. Vascular endothelial growth factor: its prognostic, predictive, and therapeutic implications. Lancet Oncol, 2001, 2(11): 667-673.
9. Shih CH, Ozawa S, Ando N, et al. Vascular endothelial growth factor expression predicts outcome and lymph node metastasis in squamous cell carcinoma of the esophagus. Clin Cancer Res, 2000, 6(3): 1161-1168.
10. Kitadai Y, Haruma K, Tokutomi T, et al. Significance of vessel count and vascular endothelial growth factor in human esophageal carcinomas. Clin Cancer Res, 1998, 4(9): 2195-2200.
11. Inoue K, Ozeki Y, Suganuma T, et al. Vascular endothelial growth factor expression in primary esophageal squamous cell carcinoma. Association with angiogenesis and tumor progression. Cancer, 1997, 79(2): 206-213.
12. Kleespies A, Guba M, Jauch KW, et al. Vascular endothelial growth factor in esophageal cancer. J SurgOncol, 2004, 87(2): 95-104.
13. William PT, David PK, David HI, et al. Targeted Therapies for Esophageal Cancer. The Oncologist, 2005, 10(8): 590-601.
14. 李寶江, 賈王生, 臧長運. 食管癌組織VEGF的表達與腫瘤血管生成的關系. 實用癌癥雜志, 2000, 15(6): 583-584.
15. Poon RTP, Fan ST, Wong J, et al. Clinical significance of angiogenesis in gastrointestinal cancers – a target of novel prognostic and therapeutic approaches. Ann Surg, 2003, 238(1): 9-28.
16. Nicosia R. What is the role of vascular endothelial growth factorrelated molecules in tumor angiogenesis. Am J Pathol, 1998, 153(1): 11-16.
17. Miroslaw K, Oksana K, Robert M, et al. Serum vascular endothelial growth factors C and D in patients with oesophageal cancer. Eur J Cardio-thoracic Surg, 2010, 38(3): 260-267.
18. Cavazzola LT, Rosa AR, Schirmer CC, et al. Immunohistochemical evaluation for P53 and VEGF (Vascular Endothelial Growth Factor) is not prognostic for long term survival in end stage esophageal adenocarcinoma. Rev Col Bras Cir, 2009, 36(1): 24-34.
19. Koide N, Nishio A, Hiraguri M, et al. Coexpression of vascular endothelial growth factor and p53 protein in squamous cell carcinoma of the esophagus. Am J Gastroenterol, 2001, 96(6): 1733-1740.
20. Shih CH, Ozawa S, Ando N, et al. Vascular endothelial growth factor expression predicts outcome and lymph node metastasis in squamous cell carcinoma of the esophagus. Clin Cancer Res, 2000, 6(3): 1161-1168.
21. Rosa AR, Schirmer CC, Gurki RR, et al. Prognostic value of p53 protein expression and vascular endothelial growth factor expression in resected squamous cell carcinoma of theesophagus. Dis Esophagus, 2003, 16(2): 112-118.
22. Shimada H, Takeda A, Nabeya Y, et al. Clinical significance of serum vascular endothelial growth factor in esophageal squamous cell carcinoma. Cancer, 2001, 92(3): 663-669.
23. 季衛忠, 顧汝軍. 食管癌患者手術治療前后血清IGF-I、VEGF和TSGF檢測的臨床意義. 放射免疫學雜志, 2011, 24(5): 496-497.
24. Kimura H, Kato H, Tanaka N, et al. Preoperative serum vascular endothelial growth factor-C (VEGF-C) levels predict recurrence in patients with esophageal cancer. Anticancer Res, 2008, 28(1A): 165-169.
25. Krzystek-Korpacka M, Matusiewicz M, Diakowska D, et al. Up-regulation of VEGF-C secreted by cancer cells and not VEGF-A correlates with clinical evaluation of lymph node metastasis in esophageal squamous cell carcinoma (ESCC). Cancer Lett, 2007, 249(2): 171-177.
26. Naumnik W, Izycki T, Swidzin´ska E, et al. Serumlevels of VEGF-C, VEGF-D, and sVEGF-R2 in patients with lung cancer during chemotherapy. Oncol Res, 2007, 16(9): 445-451.
27. Moundhri MS, Shukaili A, Nabhani M, et al. Measurement of circulating levels of VEGF-A, -C, and -D and their receptors, VEGFR-1 and -2 in gastric adenocarcinoma. World J Gastroenterol, 2008, 14(24): 3879-3883.
28. Des GG, Uzzan B, Nicolas P, et al. Microvessel density and VEGF expression are prognostic factors in colorectal cancer: Meta-analysis of the literature. Br J Cancer, 2006, 94(12): 1823-1832.
29. Li C, Zang J, Li XS, et al. Prognostic role of vascular endothelial growth factor in oral carcinoma: a meta analysis. West China Journal of Stomatology, 2011, 29(1): 39-43.
30. Chen J, Li T, Wu Y, et al. Prognostic significance of vascular endothelial growth factor expression in gastric carcinoma: a meta-analysis. J Cancer Res ClinOncol, 2011, 137(12): 1799-1812.
31. Schoenleber SJ, Kurtz DM, Talwalkar JA, et al. Prognostic role of vascular endothelial growth factor in hepatocellular carcinoma: Systematic review and meta-analysis. Br J Cancer, 2009, 100(9): 1385-1392.
32. Veikkola T, Alitalo K. VEGFS, receptors and angiogenesis. Semin Cancer Bio, 1999, 9(3): 211-220.
33. Jeltsch M, Kaipainen A, Joukov V, et al. Hyperplasia of lymphatic vessels in VEGF-Ctransgenicmice. Science, 1997, 277(5325): 463.
34. Chen M, Cai E, Huang J, et al. Prognostic Value of Vascular Endothelial Growth Factor Expression in Patients with Esophageal Cancer: ASystematic Review and Meta-analysis. Cancer Epidemiol Biomarkers Prev, 2012, 21(7): 1126-1134.
35. Akemi I, Hiromitsu M, Natsuya K, et al. Intratumorallymphangiogenesis of esophageal squamouscell carcinoma and relationship with regulatory factorsand prognosis. Pathology International, 2008, 58(10): 611-619.
36. Ching T, Shih CL, Ho J, et al. Expression of hypoxia-inducible factor(HIF)-1α and vascular endothelial growthfactor (VEGF)-D as outcome predictors inresected esophageal squamous cell carcinoma. Disease Markers, 2008, 25(3): 141-148.
37. Shimada H, Hoshino T, Okazumi S, et al. Expression of angiogenic factors predicts response tochemoradiotherapy and prognosis of oesophageal squamous cellcarcinoma. Br J Cancer, 2002, 86(4): 552-557.
38. Joon YC, Kee-Taek J, Young MS, et al. Prognostic Significance of Vascular Endothelial GrowthFactor Expression and Microvessel Density in EsophagealSquamous Cell Carcinoma: Comparison With PositronEmission Tomography. Annals of Surgical Oncology, 2006, 13(8): 1054-1062.
39. Myung J, Se-Jin J, Yong W, et al. Clinical Prognostic Values of Vascular Endothelial Growth Factor,Microvessel Density, and p53 Expression in Esophageal Carcinomas. J Korean Med Sci, 2002, 17(2): 201-207.
40. Liu P, Chen W, Zhu H, et al. Expression of VEGF-C Correlates with a Poor Prognosis Basedon Analysis of Prognostic Factors in 73 Patients with EsophagealSquamous Cell Carcinomas. Jpn J ClinOncol, 2009, 39(10): 644-650.
41. Tatsuya T, Hideyuki I, Yoshiyuki K, et al. Vascular endothelial growth factor C and D expression correlates with lymph node metastasis and poor prognosis in patients with resected esophageal cancer. J Experimental Clin Cancer Research, 2010, 29: 83.
42. Okazawa T, Yoshida T, Shirai Y, et al. Expression of Vascular EndothelialGrowth Factor C is a Prognostic Indicatorin Esophageal Cancer. Hepato-Gastroenterology, 2008, 55(86-87): 1503-1508.
43. Sun ZG, Wang Z, Liu XY, et al. Mucin 1 and Vascular Endothelial Growth Factor C ExpressionCorrelates with Lymph Node Metastatic Recurrence in Patientswith N0 Esophageal Cancer After Ivor-Lewis Esophagectomy. World J Surg, 2011, 35(1): 70-77.
44. Kozlowski M, Naumnik W, Niklinski J, et al. Vascular endothelial growth factor C and D expression correlates with lymph node metastasis and poor prognosis in patients with resected esophageal cancer. Neoplasma, 2011, 58(4): 311-319.
45. Reigetsu Y, Yoshinori F, Kenji K, et al. Cyclooxygenase-2 expression after preoperative chemoradiotherapy correlates with more frequent esophageal cancer recurrence. World J Gastroenterol, 2007, 13(16): 2283-2288.
46. Lisa MM, Douglas GA, Willi S, et al. Reporting recommendations for tumor MARKer prognostic studies (REMARK). Nature, 2005, 2(8): 416-422.

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血管內皮生長因子與食管癌預后相關性的Meta分析

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《中國循證醫學雜志》

血管內皮生長因子與食管癌預后相關性的Meta分析

摘要 全文 圖表 視頻 參考文獻 施引文獻 補充材料

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