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

• Published in: The International journal of biological markers Vol. 19; no. 4; pp. 262 - 267
• Main Authors: ARUN, C, DECATRIS, M, HEMINGWAY, D. M, LONDON, N. J. M, O'BYRNE, K. J
• Format: Journal Article
• Language: English
• Published: Milano Wichtig 01.10.2004
• Subjects: Analytical, structural and metabolic biochemistry; Biological and medical sciences; Biomarkers, Tumor; Carcinoma, Non-Small-Cell Lung - blood; Carcinoma, Non-Small-Cell Lung - metabolism; Cell Line, Tumor; Endothelin-1 - biosynthesis; Endothelin-1 - blood; Enzyme-Linked Immunosorbent Assay; Female; Fundamental and applied biological sciences. Psychology; Humans; Immunohistochemistry; In Situ Hybridization; Investigative techniques, diagnostic techniques (general aspects); Lung Neoplasms - blood; Lung Neoplasms - metabolism; Male; Medical sciences; Neovascularization, Pathologic; Prognosis; RNA, Messenger - metabolism; Time Factors; Lung disease; Prognosis; Respiratory disease; Lung cancer; Clinical biology; Bronchus disease; Biochemistry; Endothelin 1; Malignant tumor; Molecular biology; non-small cell lung carcinoma
• ISSN: 0393-6155; 1724-6008
• DOI: 10.1177/172460080401900402

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.