The Role of Serum Angiopoietin-2 Levels in Progression and Prognosis of Lung Cancer: A Meta-analysis

Overview

Journal Medicine (Baltimore)

Specialty General Medicine

Date 2017 Sep 15

PMID 28906403

Citations 20

Authors

Yuyang Xu

Yingyi Zhang

Zihuai Wang

Nan Chen

Jian Zhou

Lunxu Liu

Affiliations

Soon will be listed here.

Abstract

Background: Angiogenesis is an essential process in the development and progression of malignant tumors including lung cancer, in which angiopoietin-2 (Ang-2) plays an important role. The objective of this study was to assess the prognostic value of serum Ang-2 levels in patients with lung cancer.

Methods: A comprehensive systematic electronic search was performed in the Pubmed, Embase, Web of Science, china national knowledge infrastructure, and VIP databases update to October, 2016 (qikan.cqvip.com). Literatures examining the relevance of serum Ang-2 levels to progression and prognosis of lung cancer were eligible for our study. Standardized mean differences (SMD) with 95% confidence interval (95% CI) and a P value were applied to compare continuous variables, and hazard ratio (HR) with 95% CI as well as P value were applied for prognostic role.

Results: Twenty studies with 1911 patients met the eligibility criteria. Among them, 7 studies with 575 patients with lung cancer assessed the association between expression of serum Ang-2 and prognosis. According to our results, higher levels of serum Ang-2 were associated with the later stage of tumor. Serum Ang-2 levels were significantly lower in stage I than in stage II (SMD: -0.51; 95% CI: -0.75 to -0.27; P < .001), in stage II than in stage III (SMD: -0.52; 95% CI: -0.80 to -0.24; P < .001), in stage III than in stage IV (SMD: -0.58; 95% CI: -0.93 to -0.23; P = .001). In addition, serum Ang-2 levels were higher in patients with lymph node metastasis (SMD: 1.06; 95% CI, 0.57-1.56; P < .001). Meanwhile, patients with lung cancer with higher levels of serum Ang-2 were associated with a significant poorer prognosis when compared to those with lower serum Ang-2 levels (HR: 1.64; 95% CI: 1.20-2.25; P = .002), and this role was further detected when stratified by ethnicity and histological type.

Conclusions: This systematic review and meta-analysis suggested that serum Ang-2 levels might be a potential predictor for staging, and were associated with prognosis of lung cancer.

Citing Articles

Dynamics of VEGF-А, Аngiopoietin-2 and HIF-1α Levels in Patients with Brain Metastases Treated with Cyberknife Radiosurgery.

Popov V, Raycheva G, Grudeva-Popova Z Technol Cancer Res Treat. 2025; 24():15330338251313945.

PMID: 39801284 PMC: 11726525. DOI: 10.1177/15330338251313945.

Advances in lymphatic metastasis of non-small cell lung cancer.

Zhang X, Ma L, Xue M, Sun Y, Wang Z Cell Commun Signal. 2024; 22(1):201.

PMID: 38566083 PMC: 10986052. DOI: 10.1186/s12964-024-01574-1.

The possible dual role of Ang-2 in the prognosis of pancreatic cancer.

Roos-Mattila M, Kaprio T, Mustonen H, Hagstrom J, Saharinen P, Haglund C Sci Rep. 2023; 13(1):18725.

PMID: 37907568 PMC: 10618172. DOI: 10.1038/s41598-023-45194-0.

Ang-2 is a potential molecular marker for lymphatic metastasis and better response to bevacizumab therapy in ovarian cancer.

Volk A, Legler K, Hamester F, Kuerti S, Eylmann K, Rossberg M J Cancer Res Clin Oncol. 2023; 149(17):15957-15967.

PMID: 37684509 PMC: 10620258. DOI: 10.1007/s00432-023-05354-1.

Baseline Ang-2 Serum Levels as a Predictive Factor for Survival in NSCLC and SCLC.

Nikolakopoulou A, Tsakogiannis D, Zagouri F, Zografos E, Tzioga L, Stratakos G Life (Basel). 2022; 12(12).

PMID: 36556457 PMC: 9786126. DOI: 10.3390/life12122092.

References

Takanami I . Overexpression of Ang-2 mRNA in non-small cell lung cancer: association with angiogenesis and poor prognosis. Oncol Rep. 2004; 12(4):849-53. View

Maisonpierre P, Suri C, Jones P, Bartunkova S, Wiegand S, Radziejewski C . Angiopoietin-2, a natural antagonist for Tie2 that disrupts in vivo angiogenesis. Science. 1997; 277(5322):55-60. DOI: 10.1126/science.277.5322.55. View

Suri C, Jones P, Patan S, Bartunkova S, Maisonpierre P, Davis S . Requisite role of angiopoietin-1, a ligand for the TIE2 receptor, during embryonic angiogenesis. Cell. 1996; 87(7):1171-80. DOI: 10.1016/s0092-8674(00)81813-9. View

Kabalak P, Ciledag A, Demir N, Celik G, Yuksel C, Koycu G . Prognostic significance of serum vascular endothelial growth factor and Angiopoietin-2 in patients with lung cancer. Tuberk Toraks. 2015; 63(2):71-7. DOI: 10.5578/tt.9015. View

Xu C, Wang W, Wang Y, Zhang X, Yan J, Yu L . Serum Angiopoietin-2 as a Clinical Marker for Lung Cancer in Patients with Solitary Pulmonary Nodules. Ann Clin Lab Sci. 2016; 46(1):60-4. View

Yuan A, Yang P, Yu C, Lee Y, Yao Y, Chen C . Tumor angiogenesis correlates with histologic type and metastasis in non-small-cell lung cancer. Am J Respir Crit Care Med. 1995; 152(6 Pt 1):2157-62. DOI: 10.1164/ajrccm.152.6.8520790. View

Coelho A, Araujo A, Gomes M, Catarino R, Bonifacio Andrade E, Lopes A . Combined Ang-2 and VEGF serum levels: holding hands as a new integral biomarker in non-small-cell lung cancers. Future Oncol. 2015; 11(24):3233-42. DOI: 10.2217/fon.15.207. View

Choi S, Chae E, Shin S, Kim E, Kim J, Lee H . Comparisons of clinical outcomes in patients with and without a preoperative tissue diagnosis in the persistent malignant-looking, ground-glass-opacity nodules. Medicine (Baltimore). 2016; 95(34):e4359. PMC: 5400311. DOI: 10.1097/MD.0000000000004359. View

Yancopoulos G, Davis S, Gale N, Rudge J, Wiegand S, Holash J . Vascular-specific growth factors and blood vessel formation. Nature. 2000; 407(6801):242-8. DOI: 10.1038/35025215. View

10.

Fawzy A, Gaafar R, Kasem F, Ali S, Elshafei M, Eldeib M . Importance of serum levels of angiopoietin-2 and survivin biomarkers in non-small cell lung cancer. J Egypt Natl Canc Inst. 2013; 24(1):41-5. DOI: 10.1016/j.jnci.2011.12.006. View

11.

Etoh T, Inoue H, Tanaka S, Barnard G, Kitano S, Mori M . Angiopoietin-2 is related to tumor angiogenesis in gastric carcinoma: possible in vivo regulation via induction of proteases. Cancer Res. 2001; 61(5):2145-53. View

12.

Parmar M, Torri V, Stewart L . Extracting summary statistics to perform meta-analyses of the published literature for survival endpoints. Stat Med. 1999; 17(24):2815-34. DOI: 10.1002/(sici)1097-0258(19981230)17:24<2815::aid-sim110>3.0.co;2-8. View

13.

Wheatley-Price P, Shepherd F . Targeting angiogenesis in the treatment of lung cancer. J Thorac Oncol. 2008; 3(10):1173-84. DOI: 10.1097/JTO.0b013e318187220f. View

14.

Wong M, Chan S, Fu K, Leung S, Cheung N, Yuen S . The angiopoietins, tie2 and vascular endothelial growth factor are differentially expressed in the transformation of normal lung to non-small cell lung carcinomas. Lung Cancer. 2000; 29(1):11-22. DOI: 10.1016/s0169-5002(00)00118-5. View

15.

Aberle D, Adams A, Berg C, Black W, Clapp J, Fagerstrom R . Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med. 2011; 365(5):395-409. PMC: 4356534. DOI: 10.1056/NEJMoa1102873. View

16.

Park J, Park K, Kim Y, Sheen S, Lee K, Lee H . Serum angiopoietin-2 as a clinical marker for lung cancer. Chest. 2007; 132(1):200-6. DOI: 10.1378/chest.06-2915. View

17.

Xuan Z, Zhang S, Yuan S, Wang W, Yu J . Prognostic value of angiopoietin-2 in non-small cell lung cancer patients: a meta-analysis. World J Surg Oncol. 2016; 14(1):237. PMC: 5010677. DOI: 10.1186/s12957-016-0992-4. View

18.

Mazzieri R, Pucci F, Moi D, Zonari E, Ranghetti A, Berti A . Targeting the ANG2/TIE2 axis inhibits tumor growth and metastasis by impairing angiogenesis and disabling rebounds of proangiogenic myeloid cells. Cancer Cell. 2011; 19(4):512-26. DOI: 10.1016/j.ccr.2011.02.005. View

19.

Zhang C, Ge S, Yang N, Zhang J, Tian D . Elevated Serum Level of Angiopoietin-2 as a Potential Marker for Poor Prognosis in Small Cell Lung Cancer. Tohoku J Exp Med. 2015; 236(4):305-9. DOI: 10.1620/tjem.236.305. View

20.

Sessa C, Guibal A, Del Conte G, Ruegg C . Biomarkers of angiogenesis for the development of antiangiogenic therapies in oncology: tools or decorations?. Nat Clin Pract Oncol. 2008; 5(7):378-91. DOI: 10.1038/ncponc1150. View