ORIGINAL ARTICLE
Prognostic value of tumour tissue ANG-1 expression and Ang-1 concentration in patients with non-small-cell lung cancer
1
Chair and Department of Medical and Molecular Biology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, Katowice, Poland
2
Department of Basic Medical Sciences, Faculty of Health Sciences in Bytom, Medical University of Silesia, Katowice, Poland
3
Chair and Department of Environmental Medicine and Epidemiology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, Katowice, Poland
4
John Paul II Hospital of Oncology, General Surgery Ward, Bielsko-Biala, Poland
Submission date: 2021-09-03
Final revision date: 2022-01-17
Acceptance date: 2022-06-28
Publication date: 2022-06-29
Pol J Pathol 2022;73(1):6-13
KEYWORDS
TOPICS
ABSTRACT
Tumor cells stimulate local angiogenesis, resulting in their further multiplication and spread. Angiogenesis is a multifaceted process in which angiopoietins parti-
cipate. Angiopoietin-1 (Ang-1) through its receptor Tie2 stimulates endothelial
cell survival and the maintenance of the endothelial barrier. These phenomena can support tumour growth by promoting angiogenesis. On the other hand, overproduction of Ang-1 triggers endothelium stability and can lead to angiogenesis inhibition. Because of the ambiguous role of Ang-1, we decided to determine its clinical significance in patients with resectable NSCLC.
In a group of 47 patients, tumours and the adjacent non-cancerous tissues were assessed for ANG-1 mRNA expression (using Q-RT-PCR analysis) and Ang-1 concentration (by enzyme-linked immunosorbent assay) together with clinical parameters and the five-year survival rate. ANG-1 expression and Ang-1 concentration were higher in tumour-free tissue, showing no differences between histological types of NSCLC, clinical stage or grading and seemed not to determine the five-year survival. ANG-1 expression and Ang-1 concentration in tumour and tumour-free tissues in patients with NSCLC seem not to be useful as factors supporting either diagnostics or prognosis.
cipate. Angiopoietin-1 (Ang-1) through its receptor Tie2 stimulates endothelial
cell survival and the maintenance of the endothelial barrier. These phenomena can support tumour growth by promoting angiogenesis. On the other hand, overproduction of Ang-1 triggers endothelium stability and can lead to angiogenesis inhibition. Because of the ambiguous role of Ang-1, we decided to determine its clinical significance in patients with resectable NSCLC.
In a group of 47 patients, tumours and the adjacent non-cancerous tissues were assessed for ANG-1 mRNA expression (using Q-RT-PCR analysis) and Ang-1 concentration (by enzyme-linked immunosorbent assay) together with clinical parameters and the five-year survival rate. ANG-1 expression and Ang-1 concentration were higher in tumour-free tissue, showing no differences between histological types of NSCLC, clinical stage or grading and seemed not to determine the five-year survival. ANG-1 expression and Ang-1 concentration in tumour and tumour-free tissues in patients with NSCLC seem not to be useful as factors supporting either diagnostics or prognosis.
REFERENCES (38)
2.
Torre LA, Bray F, Siegel RL, et al. Global cancer statistics, 2012. CA Cancer J Clin 2015; 265: 87-108.
3.
Ferlay J, Soerjomataram I, Dikshit R, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 2015; 136: E359-386.
4.
Osmani L, Askin F, Gabrielson E, et al. Current WHO guidelines and the critical role of immunohistochemical markers in the subclassification of non-small cell lung carcinoma (NSCLC): Moving from targeted therapy to immunotherapy. Semin Cancer Biol 2018; 52: 103-109.
5.
Xie FJ, Lu HY, Zheng QQ, et al. The clinical pathological characteristics and prognosis of FGFR1 gene amplification in non-small-cell lung cancer: a meta-analysis. Onco Targets Ther 2016; 9: 171-181.
6.
Howlader N, Noone AM, Krapcho M, et al. SEER cancer statistics review, 1975–2012. National Cancer Institute, Bethesda, Maryland, 2015.
7.
Herbst RS, Morgensztern D, Boshoff C. The biology and management of non-small cell lung cancer. Nature 2018; 553: 446-454.
8.
Ferrara N. VEGF and the quest for tumour angiogenesis factors. Nat Rev Cancer 2002; 2: 795-803.
9.
Holopainen T, Huang H, Chen C, et al. Angiopoietin-1 overexpression modulates vascular endothelium to facilitate tumor cell dissemination and metastasis establishment. Cancer Res 2009; 69: 4656-4664.
10.
He Y, Karpanen T, Alitalo K. Role of lymphangiogenic factors in tumor metastasis. Biochim Biophys Acta 2004; 1654: 3-12.
11.
Nishida N, Yano H, Nishida T, et al. Angiogenesis in cancer. Vasc Health Risk Manag 2006; 2: 213-219.
12.
Park JH, Choi H, Kim YB, et al. Serum angiopoietin-1 as a prognostic marker in resected early stage lung cancer. Lung Cancer 2009; 66: 359-364.
13.
Dong Z, Chen J, Yang X, et al. Ang-2 promotes lung cancer metastasis by increasing epithelial-mesenchymal transition. Oncotarget 2018; 27: 12705-12717.
14.
Tait CR, Jones PF. Angiopoietins in tumours: the angiogenic switch. J Pathol 2004; 204: 1-10.
15.
Suri C, Jones PF, Patan S, et al. Requisite role of angiopoietin-1, a ligand for the TIE2 receptor, during embryonic angiogenesis. Cell 1996; 87: 1171-1180.
16.
Hayes AJ, Huang WQ, Mallah J, et al. Angiopoietin-1 and its receptor Tie-2 participate in the regulation of capillary-like tubule formation and survival of endothelial cells. Microvasc Res 1999; 58: 224–237.
17.
Hawighorst T, Skobe M, Streit M, et al. Activation of the tie2 receptor by angiopoietin-1 enhances tumor vessel maturation and impairs squamous cell carcinoma growth. Am J Pathol 2002; 160: 1381-1392.
18.
Wong MP, Chan SY, Fu KH, 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. Lung Cancer 2000; 29: 11-22.
19.
Thomas M, Augustin HG. The role of the Angiopoietins in vascular morphogenesis. Angiogenesis 2009; 12: 125-137.
20.
Caine GJ, Blann AD, Stonelake PS, et al. Plasma angiopoietin-1, angiopoietin-2 and Tie-2 in breast and prostate cancer: a comparison with VEGF and Flt-1. Eur J Clin Invest 2003; 33: 883-890.
21.
Shirakawa K, Tsuda H, Heike Y, et al. Absence of endothelial cells, central necrosis, and fibrosis are associated with aggressive inflammatory breast cancer. Cancer Res 2001; 61: 445-451.
22.
Stratmann A, Risau W, Plate KH. Cell type-specific expression of angiopoietin-1 and angiopoietin-2 suggests a role in glioblastoma angiogenesis. Am J Pathol 1998; 153: 1459-1466.
23.
Wang J, Wu K, Zhang D, et al. Expressions and clinical significances of angiopoietin-1, -2 and Tie2 in human gastric cancer. Biochem Biophys Res Commun 2005; 337: 386-393.
24.
Mitsuhashi N, Shimizu H, Ohtsuka M, et al. Angiopoietins and Tie-2 expression in angiogenesis and proliferation of human hepatocellular carcinoma. Hepatology 2003; 37: 1105-1113.
25.
Lim W, Ridge CA, Nicholson AG, et al. The 8th lung cancer TNM classification and clinical staging system: review of the changes and clinical implications. Quant Imaging Med Surg 2018; 8: 709-718.
26.
Wang J, Wu N, Lv C. et al. Recommended changes for the 8th edition of the TNM classification for lung cancer-the findings of a single-institution evaluation. Ann Transl Med 2020; 8: 123.
27.
Livak KJ, Schmittgen TD. Analysis of relative gene expression data using Real-Time Quantitative PCR and the 2 -ΔΔCT method. Methods 2001; 25: 402-408.
28.
Lowry OH, Rosebrough NJ, Farr L, et al. Protein measurement with the folin phenol reagent. J Biol Chem 1951; 193: 265-275.
29.
Naylor EC, Desani JK, Chung PK. Targeted therapy and immunotherapy for lung cancer. Surg Oncol Clin N Am 2016; 25: 601-609.
30.
Birim O, Kappetein AP, Waleboer M, et al. Long-term survival after non-small cell lung cancer surgery: development and validation of a prognostic model with a preoperative and postoperative mode. J Thorac Cardiovasc Surg 2006; 132: 491-498.
31.
Fujimoto T, Cassivi SD, Yang P, et al. Completely resected N1 non–small cell lung cancer: Factors affecting recurrence and long-term survival. J Thorac Cardiovasc Surg 2006; 132: 499-506.
32.
Fukuhara S, Sako K, Noda K, et al. Tie2 is tied at the cell-cell contacts and to extracellular matrix by Angiopoietin-1. Exp Mol Med 2009; 41: 133-139.
33.
Huang H, Bhat A, Woodnutt G, et al. Targeting the ANGPT–TIe2 pathway in malignancy. Nat Rev Cancer 2010; 10: 575-585.
34.
Takahama M, Tsutsumi M, Tsujiuchi T, et al. Enhanced expression of Tie2, its ligand angiopoietin-1, vascular endothelial growth factor, and CD31 in human non-small cell lung carcinomas. Clin Cancer Res 1999; 5: 2506-2510.
35.
Reinmuth N, Piegelbrock E, Raedel M, et al. Prognostic significance of vessel architecture and vascular stability in non-small cell lung cancer. Lung Cancer 2007; 55: 53-60.
36.
Andersen S, Donnem T, Al-Shibli K, et al. Prognostic impacts of angiopoietins in NSCLC tumor cells and stroma: VEGF-A impact is strongly associated with Ang-2. PLoS One 2011; 6(5): e19773.
37.
Huang Z, Bao SD. Roles of main pro- and anti-angiogenic factors in tumor angiogenesis. World J Gastroenterol 2004; 10: 463-470.
38.
Tabchi S, Blais N. Antiangiogenesis for advanced non-small-cell lung cancer in the era of immunotherapy and personalized medicine. Front Oncol 2017; 29: 7-52.
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