Endothelin-1 is a novel prognostic factor in non-small cell lung cancer

Arun, C., DeCatris, M., Hemingway, D. M., London, N. J. M., & O'Byrne, Kenneth J. (2004) Endothelin-1 is a novel prognostic factor in non-small cell lung cancer. International Journal of Biological Markers, 19(4), pp. 262-267.

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Abstract

Endothelin-1 (ET-1) is a potent vasoactive peptide and a hypoxia-inducible angiogenic growth factor associated with the development and growth of solid tumours. This study evaluated the expression of big endothelin-1 (big ET-1), a stable precursor of ET-1, and ET-1 in non-small cell lung cancer (NSCLC). Big ET-1 expression was evaluated in paraffin-embedded tissue sections from 10 NSCLC tumours using immunohistochemistry and in situ hybridisation. The production of big ET-1 and ET-1 was studied in six established NSCLC cell lines. The plasma concentrations of big ET-1 were measured in 30 patients with proven NSCLC prior to chemotherapy by means of a sandwich enzyme-linked immunoassay and compared to levels in 20 normal controls. Big ET-1 immunostaining was detected in the cancer cells of all tumours studied. Using in situ hybridisation, tumour cell big ET-1 mRNA expression was demonstrated in all samples. All six NSCLC cell lines expressed ET-1, with big ET-1 being detected in three. The median big ET-1 plasma level in patients with NSCLC was 5.4 pg/mL (range 0-22.7 pg/mL) and was significantly elevated compared to median big ET-1 plasma levels in controls, 2.1 pg/mL (1.2-13.4 pg/mL) (p=0.0001). Furthermore, patients with plasma big ET-1 levels above the normal range (upper tertile) had a worse outcome (p=0.01). In conclusion, big ET-1/ET-1 is expressed by resected NSCLC specimens and tumour cell lines. Plasma big ET-1 levels are elevated in NSCLC patients compared to controls with levels >7.8 pg/mL being associated with a worse outcome. The development of selective ET-1 antagonists such as Atrasentan indicates that ET-1 may be a therapeutic target in NSCLC. © 2004 Wichtig Editore.

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21 citations in Scopus
19 citations in Web of Science®
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ID Code: 64808
Item Type: Journal Article
Refereed: Yes
Keywords: Angiogenesis, Non-small cell lung cancer, Prognosis, Tumour marker, atrasentan, big endothelin 1, endothelin 1, messenger RNA, paraffin, protein precursor, adult, aged, article, cancer cell culture, cancer chemotherapy, cancer surgery, clinical article, controlled study, correlation analysis, drug research, drug selectivity, drug targeting, enzyme immunoassay, enzyme linked immunosorbent assay, female, gene expression, human, human cell, human tissue, immunohistochemistry, in situ hybridization, lung non small cell cancer, male, normal value, protein blood level, protein expression, protein synthesis, statistical significance, tissue section, tumor cell, tumor cell line, Carcinoma, Non-Small-Cell Lung, Cell Line, Tumor, Endothelin-1, Enzyme-Linked Immunosorbent Assay, Humans, Lung Neoplasms, Neovascularization, Pathologic, RNA, Messenger, Time Factors, Tumor Markers, Biological
ISSN: 0393-6155
Divisions: Current > Schools > School of Biomedical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2004 Wichtig Editore Srl
Deposited On: 26 Nov 2013 01:18
Last Modified: 07 Jan 2014 03:53

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