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Clinical Cancer Research Vol. 9, 59-67, January 2003
© 2003 American Association for Cancer Research

Molecular Oncology, Markers, Clinical Correlates

Identification of Osteopontin as a Prognostic Plasma Marker for Head and Neck Squamous Cell Carcinomas1

Quynh-Thu Le2, Patrick D. Sutphin, Soumya Raychaudhuri, Sheue Ching T. Yu, David J. Terris, Ho Sheng Lin, Bert Lum, Harlan A Pinto, Albert C. Koong and Amato J. Giaccia

Department of Radiation Oncology, Center for Clinical Science Research-South, Stanford, California 94305-5152 [Q-T. L., P. D. S., S. R., S. C. T. Y., A. C. K., A. J. G.], and Departments of Otolaryngology [H. S. L., D. J. T.] and Medicine [B. L. H. A. P.], Stanford University, Stanford, California 94305

Purpose: Tumor hypoxia modifies treatment efficacy and promotes tumor progression. Here, we investigated the relationship between osteopontin (OPN), tumor pO2, and prognosis in patients with head and neck squamous cell carcinomas (HNSCC).

Experimental Design: We performed linear discriminant analysis, a machine learning algorithm, on the NCI-60 cancer cell line microarray expression database to identify a gene profile that best distinguish cell lines with high Von-Hippel Lindau (VHL) gene expression, an important regulator of hypoxia-related genes, from those with low expression. Plasma OPN levels in 15 volunteers, 31 VHL patients, and 54 HNSCC patients were quantitatively measured by ELISA. The relationships between plasma OPN levels, tumor pO2 as measured by the Eppendorf microelectrode, freedom from relapse (FFR), and survival in HNSCC patients were evaluated.

Results: Microarray analysis indicated that OPN gene expression inversely correlated with that of VHL. These findings were confirmed by Northern blot analysis. ELISA studies and Western blot in a HNSCC cell line demonstrated that hypoxia exposure resulted in increased OPN secretion. Patients with VHL syndrome had significantly higher plasma OPN levels than healthy volunteers. Plasma OPN level inversely correlated with tumor pO2 (P = 0.003, r = -0.42). OPN levels correlated with clinical outcomes. The 1-year FFR and survival rates were 80 and 100%, respectively, for patients with OPN levels <=450 ng/ml and 43 and 63%, respectively, for levels >450 ng/ml (P = 0.002 and 0.0005). Multivariate analysis revealed that OPN was an independent predictor for FFR and survival.

Conclusions: Plasma OPN levels appeared to correlate with tumor hypoxia in HNSCC patients and may serve as noninvasive tests to identify patients at high risk for tumor recurrence.


Commentary

Commentary re: Q-T. Le et al., Identification of Osteopontin as a Prognostic Marker for Head and Neck Squamous Cell Carcinomas. Clin. Cancer Res., 9: 31–32, 2003.
David T. Denhardt
Clin. Cancer Res. 2003 9: 31-32. [Full Text] [PDF]



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D. T. Denhardt
Commentary re: Q-T. Le et al., Identification of Osteopontin as a Prognostic Marker for Head and Neck Squamous Cell Carcinomas. Clin. Cancer Res., 9: 31-32, 2003.
Clin. Cancer Res., January 1, 2003; 9(1): 31 - 32.
[Full Text] [PDF]


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Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
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Copyright © 2003 by the American Association for Cancer Research.