Angiogenic factors as prognostic markers in neuroendocrine neoplasms
- 28 January 2022
- journal article
- research article
- Published by Springer Science and Business Media LLC in Endocrine
- Vol. 76 (1), 208-217
- https://doi.org/10.1007/s12020-021-02942-4
Abstract
Purpose Angiogenic markers in neuroendocrine neoplasms (NENs) have recently received increasing attention, but their clinical role remains unclear. The aim of this study was to evaluate the role of angiogenic markers in NEN aggressiveness and prognosis. Methods We performed a prospective observational study including 46 consecutive patients with proven NENs of pulmonary (45.65%) and gastro-entero-pancreatic (GEP) (54.35%) origin and 29 healthy controls. Circulating pro-angiogenic factors were measured by ELISA assay. ANG2 tissue expression was evaluated in a subgroup of ten patients by immunohistochemistry. Results The study demonstrated a significantly higher level of ANG2, ANG1, sTIE2, and PROK2 in patients affected by NENs compared to controls. In the NENs’ group we measured that: (i) ANG2 levels were higher in poorly vs well-differentiated NENs: 4.85 (2.75–7.42) vs 3.16 (1.66–6.36) ng/ml, p = 0.046 and in tumor stage 3–4 compared to stage 1–2: 4.24 (2.66–8.72) vs 2.73 (1.53–5.70), p = 0.044; (ii) ANG2 and PROK2 were significantly higher in patents with progressive disease compared to stable disease: ANG2 = 6.26 (3.98–10.99) vs 2.73 (1.65–4.36) pg/ml, p = 0.001; PROK2 = 29.19 (28.42–32.25) vs 28.37 (28.14–28.91) pg/ml, p = 0.035. Immunohistochemistry confirmed ANG2 expression in tumor specimens. Conclusions We documented higher levels of angiogenic markers in NENs, with an association between ANG2 serum levels and NENs morphology and staging. In both GEP and lung NENs, ANG2 and PROK2 are higher in case of tumor progression, suggesting a potential role as prognostic markers in NENs patients.Funding Information
- Ministero dell’Istruzione, dell’Università e della Ricerca (PRIN2017Z3N3YC)
- Sapienza Università di Roma (RM120172ADA2C4AF)
This publication has 47 references indexed in Scilit:
- Elevated Peripheral Blood Plasma Concentrations of Tie-2 and Angiopoietin 2 in Patients with Neuroendocrine TumorsInternational Journal of Molecular Sciences, 2012
- Dopamine stabilizes tumor blood vessels by up-regulating angiopoietin 1 expression in pericytes and Krüppel-like factor-2 expression in tumor endothelial cellsProceedings of the National Academy of Sciences of the United States of America, 2011
- The association of the angiopoietin/Tie-2 system with the development of metastasis and leukocyte migration in neuroendocrine tumorsEndocrine-Related Cancer, 2010
- Prokineticins in angiogenesis and cancerCancer Letters, 2010
- Role of myeloid cells in vascular endothelial growth factor-independent tumor angiogenesisCurrent Opinion in Hematology, 2010
- Angiopoietin-2 Promotes Disease Progression of Neuroendocrine TumorsClinical Cancer Research, 2010
- The angiogenic switch in carcinogenesisSeminars in Cancer Biology, 2009
- Circulating angiopoietin-2 is elevated in patients with neuroendocrine tumours and correlates with disease burden and prognosisEndocrine-Related Cancer, 2009
- Bv8/Prokineticin proteins and their receptorsLife Sciences, 2007
- New model of tumor angiogenesis: dynamic balance between vessel regression and growth mediated by angiopoietins and VEGFOncogene, 1999