Identification of osteopontin as a prognostic plasma marker for head and neck squamous cell carcinomas

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

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)59-67
Number of pages9
JournalClinical Cancer Research
Volume9
Issue number1 I
StatePublished - Jan 1 2003

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Osteopontin
Recurrence
Neoplasms
Cell Line
Carcinoma, squamous cell of head and neck
Enzyme-Linked Immunosorbent Assay
von Hippel-Lindau Disease
Gene Expression
Survival
Microelectrodes
Discriminant Analysis
Microarray Analysis
Northern Blotting
Genes
Volunteers
Healthy Volunteers
Research Design
Multivariate Analysis
Survival Rate
Western Blotting

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Le, Q. T., Sutphin, P. D., Raychaudhuri, S., Yu, S. C. T., Terris, D. J., Lin, H. S., ... Giaccia, A. J. (2003). Identification of osteopontin as a prognostic plasma marker for head and neck squamous cell carcinomas. Clinical Cancer Research, 9(1 I), 59-67.

Identification of osteopontin as a prognostic plasma marker for head and neck squamous cell carcinomas. / Le, Quynh Thu; Sutphin, Patrick D.; Raychaudhuri, Soumya; Yu, Sheue Ching T; Terris, David J.; Lin, Ho Sheng; Lum, Bert; Pinto, Harlan A.; Koong, Albert C.; Giaccia, Amato J.

In: Clinical Cancer Research, Vol. 9, No. 1 I, 01.01.2003, p. 59-67.

Research output: Contribution to journalArticle

Le, QT, Sutphin, PD, Raychaudhuri, S, Yu, SCT, Terris, DJ, Lin, HS, Lum, B, Pinto, HA, Koong, AC & Giaccia, AJ 2003, 'Identification of osteopontin as a prognostic plasma marker for head and neck squamous cell carcinomas', Clinical Cancer Research, vol. 9, no. 1 I, pp. 59-67.
Le, Quynh Thu ; Sutphin, Patrick D. ; Raychaudhuri, Soumya ; Yu, Sheue Ching T ; Terris, David J. ; Lin, Ho Sheng ; Lum, Bert ; Pinto, Harlan A. ; Koong, Albert C. ; Giaccia, Amato J. / Identification of osteopontin as a prognostic plasma marker for head and neck squamous cell carcinomas. In: Clinical Cancer Research. 2003 ; Vol. 9, No. 1 I. pp. 59-67.
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abstract = "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.",
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AU - Raychaudhuri, Soumya

AU - Yu, Sheue Ching T

AU - Terris, David J.

AU - Lin, Ho Sheng

AU - Lum, Bert

AU - Pinto, Harlan A.

AU - Koong, Albert C.

AU - Giaccia, Amato J.

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N2 - 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.

AB - 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.

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