An evaluation of tumor oxygenation and gene expression in patients with early stage non-small cell lung cancers

Le, Q. T., Chen, E., Salim, A., Cao, H., Kong, C. S., Whyte, R., Donington, J., Cannon, W., Wakelee, H., Tibshirani, R., Mitchell, J. D., Richardson, D., O'Byrne, Kenneth J., Koong, A. C., & Giaccia, A. J. (2006) An evaluation of tumor oxygenation and gene expression in patients with early stage non-small cell lung cancers. Clinical Cancer Research, 12(5), pp. 1507-1514.

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Abstract

Background: To directly assess tumor oxygenation in resectable non - small cell lung cancers (NSCLC) and to correlate tumor pO2 and the selected gene and protein expression to treatment outcomes.

Methods: Twenty patients with resectable NSCLC were enrolled. Intraoperative measurements of normal lung and tumor pO2 were done with the Eppendorf polarographic electrode. All patients had plasma osteopontin measurements by ELISA. Carbonic anhydrase-IX (CA IX) staining of tumor sections was done in the majority of patients (n = 16), as was gene expression profiling (n = 12) using cDNA microarrays. Tumor pO2 was correlated with CA IX staining, osteopontin levels, and treatment outcomes.

Results: The median tumor pO2 ranged from 0.7 to 46 mm Hg (median, 16.6) and was lower than normal lung pO2 in all but one patient. Because both variables were affected by the completeness of lung deflation during measurement, we used the ratio of tumor/normal lung (T/L) pO2 as a reflection of tumor oxygenation. The median T/L pO 2 was 0.13. T/L pO2 correlated significantly with plasma osteopontin levels (r = 0.53, P = 0.02) and CA IX expression (P = 0.006). Gene expression profiling showed that high CD44 expression was a predictor for relapse, which was confirmed by tissue staining of CD44 variant 6 protein. Other variables associated with the risk of relapse were T stage (P = 0.02), T/L pO2 (P = 0.04), and osteopontin levels (P = 0.001).

Conclusions: Tumor hypoxia exists in resectable NSCLC and is associated with elevated expression of osteopontin and CA IX. Tumor hypoxia and elevated osteopontin levels and CD44 expression correlated with poor prognosis. A larger study is needed to confirm the prognostic significance of these factors. © 2006 American Association for Cancer Research.

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ID Code: 65184
Item Type: Journal Article
Refereed: Yes
Additional Information: Articles free to read on journal website after 12 months
Additional URLs:
Keywords: carbonate dehydratase IX, CD44v6 antigen, complementary DNA, messenger RNA, osteopontin, adult, aged, antigen expression, article, cancer survival, clinical article, enzyme linked immunosorbent assay, female, gene expression, human, human tissue, hypoxia, immunohistochemistry, intraoperative period, lung cancer, lung non small cell cancer, male, measurement, multimodality cancer therapy, oxygen tension, priority journal, Adenocarcinoma, Adenocarcinoma, Bronchiolo-Alveolar, Aged, 80 and over, Antigens, CD44, Antigens, Neoplasm, Carbonic Anhydrases, Carcinoma, Non-Small-Cell Lung, Carcinoma, Squamous Cell, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Humans, Lung, Lung Neoplasms, Middle Aged, Neoplasm Invasiveness, Neoplasm Recurrence, Local, Oligonucleotide Array Sequence Analysis, Oxygen, Prognosis, Sialoglycoproteins, Survival Rate, Tumor Markers, Biological
DOI: 10.1158/1078-0432.CCR-05-2049
ISSN: 1078-0432
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 2006 American Association for Cancer Research
Deposited On: 06 Dec 2013 03:59
Last Modified: 29 Jan 2015 05:16

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