The role of serum angiopoietin-2 levels in progression and prognosis of lung cancer: A meta-analysis

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.

Figure 1

PRISMA flow chart of literature selection. PRISMA = Preferred Reporting Items for Systematic Reviews and Meta-Analyses.

Figure 2

Forest plot of role of SMD and its 95% CI of serum Ang-2 levels between (A) stage I and II, (B) stage I and III, (C) stage I and IV, (D) stage II and III, (E)stage II and IV, and (F) stage III and IV. For each study, the estimate of SMD was plotted with squares, and the size of the square reflects the weight of the study in the meta-analysis. The horizontal line crossing the square represents the 95% CI. The diamond represents the summary SMD and 95% CI. Ang-2 = angiopoietin-2, CI = confidence interval, SMD = standardized mean differences.

Figure 3

Forest plot of role of SMD and its 95% CI of serum Ang-2 levels between lung cancer patients with and without lymph node metastasis. For each study, the estimate of SMD was plotted with squares, and the size of the square reflects the weight of the study in the meta-analysis. The horizontal line crossing the square represents the 95% CI. The diamond represents the summary SMD and 95% CI. Ang-2 = angiopoietin-2, CI = confidence interval, SMD = standardized mean differences.

Figure 4

Forest plot of role of serum Ang-2 levels on survival in lung cancer. For each study, the estimate of HR was plotted with squares, and the size of the square reflects the weight of the study in the meta-analysis. The horizontal line crossing the square represents the 95% CI. The diamond represents the summary HR and 95% CI. Ang-2 = angiopoietin-2 , CI = confidence interval, HR = hazard ratio.

Figure 5

Forest plot of role of serum Ang-2 levels on survival in lung cancer stratified by (A) ethnicity and (B) histological type. For each study, the estimate of HR was plotted with squares, and the size of the square reflects the weight of the study in the meta-analysis. The horizontal line crossing the square represents the 95% CI. The diamond represents the summary HR and 95% CI. Ang-2 = angiopoietin-2 , CI = confidence interval, HR = hazard ratio, NSCLC = non–small cell lung cancer, SCLC = small cell lung cancer.

Figure 6

Sensitivity analysis of overall survival. For each study, the circle represents the summary hazard ratio (HR) when excluded this study. The horizontal line crossing the circle represents the 95% confidence interval (CI). The short vertical at the ends of horizontal line represents the lower and upper limit of 95% CI, respectively.