Importance of serum levels of angiopoietin-2 and survivin biomarkers in non-small cell lung cancer.

BACKGROUND Angiogenesis is an essential process in cancer growth maintenance, and metastasis. Angiopoietin-2 promotes tumor angiogenesis by priming the vasculature and potentiating the effects of cytokines at the front of active neovascularization. Enhanced expression of angiopoietin-2 has been reported in lung cancer tissue. Survivin is one of the inhibitors of apoptosis protein that has been shown to play a key role in cancer progression, and in tumor angiogenesis. Also plays a key role in tumor cell resistance to anticancer agents and ionizing radiation. AIM To measure the serum levels of angiopoietin-2 and survivin as possible angiogenic factors in lung cancer patients with the assessment of their interrelationships and clinical significance. PATIENTS AND METHODS Patients with lung cancer as NSCLC (n=70) and healthy volunteers (n=10) were enrolled. Serum angiopoietin-2 and survivin concentrations were measured using enzyme-linked immunosorbent assay (ELIZA). RESULTS Median serum angiopoietin-2 levels with lung cancer (2730pg/mL) ranged from 1171 to 6541pg/mL was higher than the median of the control group (1795pg/mL) ranged from 1076 to 2730/mL, p<0.001. Median serum survivin levels were also higher in patients with lung cancer (53.0pg/mL) ranged from 39.3 to 96.3pg/mL than the median of the control group (48.8pg/mL) ranged from 38.0 to 74.6pg/mL, but did not reach statistical significance p=0.206. In all patients with lung cancer, serum angiopoietin-2 was not significantly correlated with survivin (r=0.073, p=0.657). Neither serum angiopoietin-2 nor survivin showed significant relation with the serum angiopoietin-2 or survivin levels depending on the cell types, stage progression, and metastasis among the patients with NSCLC. CONCLUSIONS Our study suggests that serum angiopoietin-2 is a useful marker for the diagnosis of NSCLC by ELIZA technique.

[1]  K. Peters Vascular endothelial growth factor and the angiopoietins: working together to build a better blood vessel. , 1998, Circulation research.

[2]  I. Yoshino,et al.  Nuclear survivin in pN2 nonsmall cell lung cancer: prognostic and clinical implications , 2009, European Respiratory Journal.

[3]  E. Felip,et al.  A novel anti-apoptosis gene: Re-expression of survivin messenger RNA as a prognosis marker in non-small-cell lung cancers. , 1999, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[4]  A. Marchetti,et al.  Survivin gene expression in early‐stage non‐small cell lung cancer , 2003, The Journal of pathology.

[5]  N. Tsuji,et al.  Detection of autoantibodies to livin and survivin in Sera from lung cancer patients. , 2005, Lung cancer.

[6]  K. Lee,et al.  Serum angiopoietin-2 as a clinical marker for lung cancer. , 2007, Chest.

[7]  Lei Wang,et al.  The role of survivin on overall survival of non-small cell lung cancer, a meta-analysis of published literatures. , 2008, Lung cancer.

[8]  Alain C. Mita,et al.  Survivin: Key Regulator of Mitosis and Apoptosis and Novel Target for Cancer Therapeutics , 2008, Clinical Cancer Research.

[9]  H. Wada,et al.  Expression of angiopoietins and its clinical significance in non-small cell lung cancer. , 2002, Cancer research.

[10]  I. Takanami Overexpression of Ang-2 mRNA in non-small cell lung cancer: association with angiogenesis and poor prognosis. , 2004, Oncology reports.

[11]  G. Dinç,et al.  Serum Her-2/neu and Survivin Levels and Their Relationship to Histological Parameters in Early-stage Breast Cancer , 2007, Journal of International Medical Research.

[12]  H. Zhen,et al.  Survivin promotes glioma angiogenesis through vascular endothelial growth factor and basic fibroblast growth factor in vitro and in vivo , 2012, Molecular carcinogenesis.

[13]  F. Tas,et al.  Serum levels of apoptosis biomarkers, survivin and TNF-alpha in nonsmall cell lung cancer. , 2008, Lung cancer.

[14]  M. Hermanová,et al.  Prognostic Significance of Anti-apoptosis Proteins Survivin and bcl-2 in Non-small Cell Lung Carcinomas: A Clinicopathologic Study of 102 Cases , 2004, Applied immunohistochemistry & molecular morphology : AIMM.

[15]  G. Yancopoulos,et al.  Vessel cooption, regression, and growth in tumors mediated by angiopoietins and VEGF. , 1999, Science.

[16]  S. Leung,et al.  The angiopoietins, tie2 and vascular endothelial growth factor are differentially expressed in the transformation of normal lung to non-small cell lung carcinomas. , 2000, Lung cancer.

[17]  Yaqoub Ashhab,et al.  The inhibitor of apoptosis protein family (IAPs): an emerging therapeutic target in cancer. , 2004, Seminars in cancer biology.

[18]  T. Dønnem,et al.  Prognostic Impacts of Angiopoietins in NSCLC Tumor Cells and Stroma: VEGF-A Impact Is Strongly Associated with Ang-2 , 2011, PloS one.

[19]  C. Mountain,et al.  Revisions in the International System for Staging Lung Cancer. , 1997, Chest.

[20]  C. Tait,et al.  Angiopoietins in tumours: the angiogenic switch , 2004, The Journal of pathology.

[21]  W. Naumnik,et al.  Serum levels of HMGB1, survivin, and VEGF in patients with advanced non-small cell lung cancer during chemotherapy. , 2010, Folia histochemica et cytobiologica.

[22]  G. Yancopoulos,et al.  New model of tumor angiogenesis: dynamic balance between vessel regression and growth mediated by angiopoietins and VEGF , 1999, Oncogene.

[23]  G. Giaccone,et al.  Nuclear localization of survivin is a positive prognostic factor for survival in advanced non-small-cell lung cancer. , 2004, Annals of oncology : official journal of the European Society for Medical Oncology.

[24]  S. Yie,et al.  Clinical significance of detecting survivin-expressing circulating cancer cells in patients with non-small cell lung cancer. , 2009, Lung cancer.

[25]  Yue Wang,et al.  非小细胞肺癌患者中Survivin抗体的临床意义及诊断价值 , 2010, Zhongguo fei ai za zhi = Chinese journal of lung cancer.

[26]  Stanley J. Wiegand,et al.  Vascular-specific growth factors and blood vessel formation , 2000, Nature.

[27]  D. Hanahan,et al.  Induction of angiogenesis during the transition from hyperplasia to neoplasia , 1989, Nature.

[28]  Sunil Singhal,et al.  Prognostic Implications of Cell Cycle, Apoptosis, and Angiogenesis Biomarkers in Non–Small Cell Lung Cancer: A Review , 2005, Clinical Cancer Research.

[29]  Houwen Li State of the art:lung cancer in China. , 2003, Annals of thoracic and cardiovascular surgery : official journal of the Association of Thoracic and Cardiovascular Surgeons of Asia.

[30]  C. Angeletti,et al.  Vascular endothelial growth factor is associated with neovascularization and influences progression of non-small cell lung carcinoma. , 1997, Clinical cancer research : an official journal of the American Association for Cancer Research.